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Bristol-Myers Squibb Enters into Separate Agreements with Biogen and Roche to License Anti-eTau and Anti-Myostatin Compounds, Respectively
By Business Wire, April 13, 2017, 06:59:00 AM EDT
Bristol-Myers Squibb to receive a combined $470M upfront, along with potential milestone payments and tiered double-digit royalties from each company
NEW YORK--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY) today announced that it has entered into two separate agreements to license BMS-986168, an anti-eTau compound in development for Progressive Supranuclear Palsy (PSP), to Biogen (NASDAQ:BIIB), and BMS-986089, an anti-myostatin adnectin in development for Duchenne Muscular Dystrophy (DMD), to Roche.
"Licensing these assets to Biogen and Roche will enable Bristol-Myers Squibb to prioritize the other promising opportunities for asset development that have advanced across our diversified portfolio," said Mike Burgess, head of Cardiovascular, Fibrosis and Immunoscience Development, Bristol-Myers Squibb. "We recognize the significant unmet medical needs for patients with PSP and with DMD, and are pleased to put the future development of these compounds into the hands of Biogen and Roche, who both have strong capabilities, focus and leadership in neurodegenerative and rare diseases."
Under the agreement to license BMS-986168, Biogen will pay to Bristol-Myers Squibb an upfront payment of $300 million with potential milestone payments of up to $410 million. Biogen also will assume all remaining obligations to the former stockholders of iPierian, Inc. related to Bristol-Myers Squibb's acquisition of the company in 2014. Under the agreement to license BMS-986089, Roche will pay to Bristol-Myers Squibb an upfront payment of $170 million with potential milestone payments of up to $205 million. Bristol-Myers Squibb will receive tiered double-digit royalties if either asset is approved and commercialized. These agreements are subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and are expected to close in the second quarter of 2017.
About BMS-986168 and BMS-986089
BMS-986168 is a monoclonal antibody designed to bind to and decrease levels of extracellular Tau (eTau) protein. It is currently being investigated as a treatment option for patients with PSP, with the potential for future development in other neurodegenerative diseases such as Alzheimer's disease.
BMS-986089 is a novel fusion protein designed to suppress myostatin, a negative regulator of muscle growth. It is currently being investigated as a treatment option for patients with DMD, and has the potential for study in other neuromuscular disorders.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compounds discussed in this release will be successfully developed or approved for any of the indications described in this release. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170413005373/en/
Source: Bristol-Myers Squibb Company
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BMY
Bristol-Myers Squibb Company (BMY) Ex-Dividend Date Scheduled for April 05, 2017
BMY
Like the proposition of approval. Thanks for the detailed explanation.
Also saw the indication of more adverse reactions:
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Opdivo, Yervoy combo scores higher survival rate for melanoma, with worse adverse events
Bristol-Myers, which has been working on bolstering its case for a combination of Opdivo and Yervoy in treating cancer, also turned up at AACR with new data that highlights improved survival rates for melanoma rates.
James Larkin, Oncologist
Oncologist James Larkin and colleagues enrolled 945 first-line patients with advanced melanoma and randomly assigned them in equal groups to nivolumab plus ipilimumab, nivolumab, or ipilimumab.
After a minimum follow-up of 28 months, investigators reported, median overall survival among those patients randomly assigned ipilimumab was 20 months. The median OS had not been reached for the nivolumab plus ipilimumab or the nivolumab plus placebo arms.
A total of 64% in the combo arm achieved two-year survival, the highest rate. The rate was 59% and 45% among those randomly assigned nivolumab plus placebo and ipilimumab alone. But the combo arm also experienced worse adverse events.
Researchers added:
A similar trend was seen for median duration of response. Median duration of response had not been reached in the nivolumab plus ipilimumab arm, while it was 31.1 months and 18.2 months for the nivolumab plus placebo arm and ipilimumab alone arm, respectively. In descriptive analyses, meaning the study was not powered for this comparison, patients randomly assigned nivolumab plus ipilimumab had a 12 percent lower risk of death compared with those randomly assigned nivolumab plus placebo.
“It is exciting to see that initial results suggest that the nivolumab plus ipilimumab combination provides favorable survival outcomes compared with ipilimumab alone,” said Larkin. “However, the combination also results in a higher rate of severe adverse events than nivolumab or ipilimumab alone, so it is important to consider this when making treatment decisions for patients.”
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https://endpts.com/aacr17-roundup-bristol-myers-merck-kgaa-and-pfizer-in-the-spotlight-marking-progress-with-checkpoints/
BMY
1 for 2 today:
FAIL
Bristol-Myers Squibb Announces Results from CheckMate -143, a Phase 3 Study of Opdivo (nivolumab) in Patients with Glioblastoma Multiforme
By Business Wire, April 03, 2017, 10:47:00 AM EDT
PRINCETON, N.J.--(BUSINESS WIRE)--
Bristol-Myers Squibb Company (NYSE:BMY) today announced that CheckMate -143, a randomized Phase 3 clinical trial evaluating the efficacy and safety of Opdivo in patients with first recurrence of glioblastoma multiforme (GBM), did not meet its primary endpoint of improved overall survival over bevacizumab monotherapy. These data will be presented on May 7, 2017 at the World Federation of Neuro-Oncology Societies (WFNOS) meeting in Zurich, Switzerland.
"GBM is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses," said Fouad Namouni, M.D., head of Oncology Development and head of Medical, Bristol-Myers Squibb. "We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our Immuno-Oncology agents can potentially improve outcomes for these patients."
CheckMate -143 was the first randomized clinical trial in GBM with a PD-1 checkpoint inhibitor. BMS has two first-line GBM clinical trials, CheckMate -498 and CheckMate -548, evaluating the combination of Opdivo with radiation therapy with or without temozolomide in O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated and methylated patients. These trials are moving forward as planned.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
U. S. FDA-APPROVED INDICATIONS FOR OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.
In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator's choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%).
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).
Checkmate Trials and Patient Populations
Checkmate 067 - advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 - advanced melanoma; Checkmate 017 - squamous non-small cell lung cancer (NSCLC); Checkmate 057 - non-squamous NSCLC; Checkmate 025 - renal cell carcinoma; Checkmate 205/039 - classical Hodgkin lymphoma; Checkmate 141 - squamous cell carcinoma of the head and neck; Checkmate 275 - urothelial carcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies - as single agents and combination regimens - for patients with cancer in Japan, South Korea and Taiwan.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Opdivo will receive regulatory approval for any additional indications. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
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Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) and Opdivo Monotherapy Significantly Improved Overall Survival Versus Yervoy Alone in Patients with Previously Untreated Advanced Melanoma
By Business Wire, April 03, 2017, 08:30:00 AM EDT
CheckMate -067 presentation marks the first disclosure of overall survival data of Opdivo in combination with Yervoy in a Phase 3 Trial
Safety profile is consistent with previous studies, with no cumulative toxicity with combination therapy or new safety signals
Bristol-Myers Squibb Company (NYSE:BMY) today announced the first overall survival (OS) data from the Phase 3 CheckMate -067 clinical trial. With a minimum follow-up of 28 months, the median OS had not yet been reached in either of the two Opdivo treatment groups and was 20 months for the Yervoy monotherapy group (95% CI: 17.1-24.6). Opdivo in combination with Yervoy and as a monotherapy reduced the risk of death 45% [hazard ratio (HR) 0.55; 95% CI: 0.42-0.72; P<0.0001] and 37% (HR 0.63; 95% CI: 0.48-0.81; P<0.0001), respectively, compared with Yervoy alone. The two-year OS rates were 64% for the Opdivo plus Yervoy combination, 59% for Opdivo alone and 45% for Yervoy alone. Results will be presented today in the press program and an oral presentation during the Update, Novel Indication, and New Immuno-oncology Clinical Trials session from 3:35 to 3:50 p.m. ET (Late-Breaking Abstract CT075) at the American Association for Cancer Research Meeting 2017 in Washington, D.C.
The updated safety data reported in this new analysis were consistent with previously reported experience, with no cumulative toxicity noted or new safety signals identified. Grade 3/4 treatment-related adverse events occurred in 58%, 21%, and 28% of the combination,Opdivo alone and Yervoy alone groups, respectively.
"It is encouraging to see such positive data from this trial, which further supports the scientific rationale to combine Immuno-Oncology agents as a potential treatment option for this aggressive form of melanoma. These CheckMate -067 survival data bolster our understanding of potential ways to combat untreated advanced melanoma and ultimately advance cancer care for patients," said James Larkin, Ph.D., FRCP, Consultant Medical Oncologist, Department of Medical Oncology, The Royal Marsden.
The proportion of patients experiencing complete responses (CR) compared to a previous 18 month follow-up analysis increased in the combination group to 17.2% from 12.1%, in the Opdivo alone group to 14.9% from 9.8%, and in the Yervoy alone group to 4.4% from 2.2%. Progression-free survival (PFS) and objective response rates (ORR) from updated analyses were both consistent with previous reports. The risk of disease progression was significantly reduced for both the combination and Opdivo monotherapy groups, 58% (HR 0.42; 95% CI: 0.34-0.51) and 46% (HR 0.54; 95% CI: 0.45-0.66), respectively, compared to Yervoy alone. The ORR for the two Opdivo groups, in combination and alone, and the Yervoy alone group was, respectively, 58.9% (95% CI: 53.3-64.4), 44.65% (95% CI: 39.1-50.3) and 19.0% (95% CI: 14.9-23.8).
"This first disclosure of overall survival data from CheckMate -067 helps to advance our understanding of the potential longer term benefits of Opdivo in combination with Yervoy in advanced melanoma, a cancer that historically has been difficult-to-treat," said Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb.
About CheckMate -067
CheckMate -067 is a Phase 3, double-blind, randomized trial that evaluated the combination of Opdivo plus Yervoy or Opdivo monotherapy versus Yervoy monotherapy in 945 patients with previously untreated advanced melanoma. Patients in the combination group (n=314) received Opdivo 1 mg/kg plus Yervoy 3 mg/kg (Q3W) for four doses followed by Opdivo 3 mg/kg every two weeks (Q2W). Patients in the Opdivo monotherapy group (n=316) received Opdivo 3 mg/kg Q2W plus placebo. Patients in the Yervoy monotherapy group (n=315) received Yervoy 3 mg/kg every three weeks for four doses plus placebo. Patients were treated until progression or unacceptable toxic effects. OS and PFS were co-primary endpoints for the trial. Secondary endpoints included ORR, efficacy by tumor PD-L1 expression level and safety.
The Opdivo plus Yervoy combination and Opdivo monotherapy provided OS benefits across clinically relevant subgroups of patients versus Yervoy alone. Specifically, in patients with BRAF mutations, the combination reduced the risk of death 57% (HR 0.43; 95% CI: 0.28-0.66) and Opdivo monotherapy reduced the risk of death 40% (HR 0.60; 95% CI: 0.40-0.89) compared to Yervoy alone. In patients without BRAF mutations (Wild-type patients), the combination reduced the risk of death 38% (HR 0.62; 95% CI: 0.48-0.80) and Opdivo monotherapy reduced the risk of death 36% (HR 0.64; 95% CI: 0.49-0.83) compared to Yervoy alone. In patients with PD-L1 expression ≥5%, Opdivo in combination with Yervoy and Opdivo monotherapy resulted in a 40% (HR 0.60; 95% CI: 0.36-1.00) and 44% (HR 0.56; 95% CI: 0.34-0.90) reduction in risk of death, respectively, compared to Yervoy alone. In patients with PD-L1 expression <5%, the combination and Opdivo monotherapy resulted in a 45% (HR 0.55; 95% CI: 0.42-0.72) and a 35% (HR 0.65; 95% CI: 0.50-0.84) reduction in risk of death, respectively, compared to Yervoy alone.
The trial was not designed to statistically compare the two Opdivo groups. However, descriptive analyses found the combination treatment provided a relative reduction in the risk of death of 12% (HR 0.88; 95% CI: 0.69-1.12) when compared with Opdivo alone and reduced the risk of death for patients expressing PD-L1 <1% by 26% (HR 0.74; 95% CI: 0.52-1.06) and PD-L1 <5% by 16% (HR 0.84; 95% CI: 0.63-1.12) when compared to Opdivo alone. Survival between the two Opdivo containing groups was similar in patients expressing PD-L1 ≥1% (HR 1.03; 95% CI: 0.72-1.48) and PD-L1 ≥5% (HR 1.05; 95% CI: 0.61-1.83).
About Metastatic Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 87,000 new diagnoses of melanoma and more than 9,700 related deaths are estimated for 2017. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 388,262, with 98,288 related deaths. Melanoma is mostly curable when treated in its early stages. However, patients in the United States diagnosed with advanced melanoma classified as Stage IV historically have a five-year survival rate of 15% to 20% and 10-year survival of about 10% to 15%.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
U.S. FDA-APPROVED INDICATIONS FOR OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.
In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO . The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator's choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%).
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).
Checkmate Trials and Patient Populations
Checkmate 067 - advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 - advanced melanoma; Checkmate 017 - squamous non-small cell lung cancer (NSCLC); Checkmate 057 - non-squamous NSCLC; Checkmate 025 - renal cell carcinoma; Checkmate 205/039 - classical Hodgkin lymphoma; Checkmate 141 - squamous cell carcinoma of the head and neck; Checkmate 275 - urothelial carcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies - as single agents and combination regimens - for patients with cancer in Japan, South Korea and Taiwan.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Opdivo or Yervoy will receive regulatory approval for an additional indication. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170403005495/en/
BMY
FOMO is bad for you. Seems like BMY has been propped up primarily by buy-out rumors only.
Also, could be low expectations from the AACR:
From Fly:
_____________________________________________-
Before the Move: Stocks to watch into meeting of cancer researchers This year's American Association for Cancer Research, or AACR, annual meeting will take place in Washington D.C. from April 1-5. Several companies are expected to present updates and new data from ongoing studies during the event. AACR ANNUAL MEETING: The AACR annual meeting 2017 will take place on April 1-5 in Washington D.C. and is expected to highlight the best cancer science and medicine from institutions all over the world. Attendees are invited to form collaborations, attend sessions outside their own areas of expertise and learn how to apply new concepts, tools and techniques to their own research, the organization has stated. DATA MAY FAVOR INCYTE: In a research note to investors ahead of the AACR meeting, BMO analyst Alex Arfaei said that the focus will be on Bristol-Myers Squibb's (BMY) Opdivo in combination with an investigational, optimized, once-daily IDO-1 inhibitor and whether the data supports its "best in class" claim. The analyst told investors that he doubts the data will appear better than Merck's (MRK) Keytruda + Incyte's (INCY) Epacadostat. Although Incyte maintains a two-year lead on other IDO-1 players, Arfaei noted that he expects the company's shares to be sensitive to clinical results for Bristol-Myers' BMS-986205 and NewLink Genetics' (NLNK) Indoximob. Overall, the analyst argued that the data at AACR are unlikely to show which IDO-1 is better, but that may be enough for Incyte since it was the first. Additionally, he believes a cost-sharing agreement with Merck and Phase 2 of Epacadostat + Keytruda in multiple solid tumor at the American Society of Clinical Oncology annual meeting remain near-term drivers of Incyte's shares.
Read more at:
http://thefly.com/landingPageNews.php?id=2528101
BMY
In EIGR @ $11.10 today. This is a $heff play (also Dan Ward):
Sheff? @SheffStation 21h21 hours ago
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$EIGR..$11.70 is going to move higher in April. One of my fav plays. Jefferies has a $28 PT & Oppenheimer a $34 PT. Many catalysts in Q2. pic.twitter.com/H9tKpLlCGw
Chart looks good, especially the MACD cross-over today and the SAR flip:
Low Float: Shs Float 8.02M
EIGR
Aeterna Zentaris Intends to File NDA with Respect to Macrilen™ in Third Quarter of 2017
Date : 03/30/2017 @ 8:00AM
Source : Business Wire
Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) (the “Company”) today announced that, following its meeting with the U.S. Food and Drug Administration (the “FDA” or the “Agency”) on March 29, 2017, the Company intends to file a new drug application (“NDA”) seeking approval of Macrilen™ (macimorelin) for the evaluation of growth hormone deficiency in adults (“AGHD”).
Commenting on the meeting, Dr. Richard Sachse, the Company’s Chief Scientific Officer, stated, “During our meeting with the FDA, the Agency stated that the clinical studies we performed with respect to Macrilen™ address the prior deficiencies mentioned in the November 2014 complete response letter. This conclusion paves the way for our re-submission of an NDA for Macrilen™, which we expect to file in the third quarter of this year. While indicating that our conclusions regarding the performance of Macrilen™ are review issues subject to an examination of the complete data set, the Agency indicated that the summary data we submitted prior to the meeting appear to support the propositions we advanced. Most importantly, the FDA specified the additional statistical analysis of existing data that would be required to further support our conclusions. We expect that we can provide those data in a compelling fashion and demonstrate that Macrilen™ is a robust, repeatable test, demonstrating adequate sensitivity and specificity and that the performance of the product would be improved by utilizing a more appropriate cut-off point.”
David A. Dodd, President and Chief Executive Officer of the Company stated, “We were encouraged by our dialogue with the FDA regarding Macrilen™. The Agency provided very helpful guidance to us that should help us in the registration process. Of course, the FDA will thoroughly review all data we provide with our NDA and make a decision regarding the approval of the product after doing so. Although there can be no assurance of approval of any NDA, we believe that we are now one important step closer to the commercialization of Macrilen™ in the U.S., providing a much needed new option and alternative to the ITT.”
About the Study
The confirmatory Phase 3 clinical study of Macrilen™, entitled Confirmatory validation of oral macimorelin as a growth hormone (GH) stimulation test (ST) for the diagnosis of adult growth hormone deficiency (AGHD) in comparison with the insulin tolerance test (ITT), was designed as a two-way crossover study with the ITT as the benchmark comparator and involved some 26 sites in the U.S. and Europe. The trial involved 157 subjects, of whom 140 completed two evaluable tests for AGHD using both Macrilen™ and the ITT. Thirty-four of the patients were evaluated using Macrilen™ a second time to measure the repeatability of the result obtained using Macrilen™ as the evaluation method. The study population consisted of 115 patients who were suspected of having AGHD as a result of the presence of one or more symptoms or risk factors. This segment of the population included a range of patients from those considered at low risk of having AGHD to those considered at high risk. The study population also included 25 healthy subjects, who had no risk of having AGHD. Under the study protocol, the evaluation of AGHD with Macrilen™ will be considered successful, if the lower bound of the two-sided 95% confidence interval (or lower bound of the one-sided 97.5% confidence interval) for the primary efficacy variables is 75% or higher for “percent negative agreement”, and 70% or higher for the “percent positive agreement”. Based on meetings with the FDA as well as the European Medicines Agency (“EMA”) and subsequent written scientific advice, the Company believes that the study meets the FDA’s and the EMA’s study-design expectations allowing U.S. and European approval if other conditions are met. Dr. Jose M. Garcia, MD, PhD, an Associate Professor of Medicine at the Puget Sound VA Hospital and the University of Washington in Seattle, was the principal investigator of the confirmatory Phase 3 clinical trial. More details about the trial are available at the following link:
https://www.clinicaltrials.gov/ct2/show/NCT02558829?term=macimorelin&rank=1.
About MacrilenTM (macimorelin)
Macimorelin, a ghrelin agonist, is an orally-active small molecule that stimulates the secretion of growth hormone. Macimorelin has been granted orphan drug designation by the FDA for diagnosis of AGHD. The Company owns the worldwide rights to this patented compound and has significant patent protection left. The Company’s U.S. composition of matter patent expires in 2022 and its U.S. utility patent runs through 2027. The Company proposes, subject to FDA approval, to market macimorelin under the tradename Macrilen™.
About AGHD
AGHD affects approximately 75,000 adults across the U.S., Canada and Europe. Growth hormone not only plays an important role in growth from childhood to adulthood, but also helps promote a hormonally-balanced health status. AGHD mostly results from damage to the pituitary gland. It is usually characterized by a reduction in bone mineral density, lean body mass, exercise capacity, and overall quality of life as well as an increase of cardiovascular risks.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a specialty biopharmaceutical company engaged in developing and commercializing novel treatments in oncology, endocrinology and women’s health. We are engaged in drug development activities and in the promotion of products for others. We recently completed Phase 3 studies of two internally developed compounds. The focus of our business development efforts is the acquisition of licenses to products that are relevant to our therapeutic areas of focus. We also intend to license out certain commercial rights of internally developed products to licensees in non-U.S. territories where such out-licensing would enable us to ensure development, registration and launch of our product candidates. Our goal is to become a growth-oriented specialty biopharmaceutical company by pursuing successful development and commercialization of our product portfolio, achieving successful commercial presence and growth, while consistently delivering value to our shareholders, employees and the medical providers and patients who will benefit from our products. For more information, visit www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made pursuant to the safe harbor provision of the U.S. Securities Litigation Reform Act of 1995, which reflect our current expectations regarding future events. Forward-looking statements may include, but are not limited to statements preceded by, followed by, or that include the words “expects,” “believes,” “intends,” “anticipates,” and similar terms that relate to future events, performance, or our results. Forward-looking statements involve known risks and uncertainties, many of which are discussed under the caption “Key Information – Risk Factors” in our most recent Annual Report on Form 20-F filed with the relevant Canadian securities regulatory authorities in lieu of an annual information form and with the U.S. Securities and Exchange Commission (“SEC”). Such statements include, but are not limited to, statements about the progress of our research, development and clinical trials and the timing of, and prospects for, regulatory approval and commercialization of our product candidates, the timing of expected results of our studies, anticipated results of these studies, statements about the status of our efforts to establish a commercial operation and to obtain the right to promote or sell products that we did not develop and estimates regarding our capital requirements and our needs for, and our ability to obtain, additional financing. Known and unknown risks and uncertainties could cause our actual results to differ materially from those in forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue our research and development projects and clinical trials, the successful and timely completion of clinical studies, the risk that safety and efficacy data from any of our Phase 3 trials may not coincide with the data analyses from previously reported Phase 1 and/or Phase 2 clinical trials, the rejection or non-acceptance of any new drug application by one or more regulatory authorities and, more generally, uncertainties related to the regulatory process (including whether or not the regulatory authorities will definitively accept the Company’s conclusions regarding Macrilen™ and approve its registration following the Company’s comprehensive review of the Phase 3 study data described elsewhere in this press release), the ability of the Company to efficiently commercialize one or more of its products or product candidates, the degree of market acceptance once our products are approved for commercialization, our ability to take advantage of business opportunities in the pharmaceutical industry, our ability to protect our intellectual property, and the potential of liability arising from shareholder lawsuits and general changes in economic conditions. Investors should consult the Company’s quarterly and annual filings with the Canadian securities commissions and the SEC for additional information on risks and uncertainties. Given these uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170330005118/en/
Aeterna Zentaris Inc.
Philip A. Theodore, 843-900-3223
Senior Vice President
ir@aezsinc.com
Letter mentioning BMY sent to Carl Icahn:
Jesse Rodriguez?Verified account
@JesseRodriguez
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Sens. Whitehouse, Warren, others send letter to @Carl_C_Icahn asking him to explain his role in the Trump admin
______________________________________
BMY
Assuming MarketBeat is up-to-date their latest rating for BMY was in October:
10/17/2016 Credit Suisse Group AG Reiterated Rating Hold $58.00 N/A
https://www.marketbeat.com/stocks/NYSE/BMY/
BMY
Not sure as to what you are questioning. I have no knowledge of the individual or the issue and cursory Googling doesn't help. But that means nothing as I don't have in-depth knowledge of BMY.
On the surface it seems that PFE is the most likely candidate for a BO of BMY.
BMY
Rumors persist:
______________________________________________________
March 27, 2017, 9:45 A.M. ET
Bristol-Myers: Maybe a Pfizer Acquisition Could Makes Sense After All?
By Ben Levisohn
Remember when Bristol-Myers Squibb (BMY) was getting hit so hard that everyone was wondering whether it would find itself acquired by another pharmaceutical, with Pfizer (PFE), Novartis (NVS), Gilead Sciences (GILD), and Roche mentioned as possible buyers? Well, that speculation just won’t die.
In a note released yesterday, Credit Suisse analyst Vamil Divan and team revisit the possibility of Pfizer taking over Bristol-Myers with their colleagues at the firm’s HOLT team…and find that it just might provide “an opportunity for value creation” after all. They explain why:
Overall, HOLT® suggests that an acquisition of BMY by PFE would have a positive impact on PFE’s return on capital profile when assuming industry average synergies for a deal of this nature. An all-cash deal (assuming PFE pays a 25% premium and can extract synergies of 30% of BMY’s operating expenses) would lead to about $5Bn or approximately $.80 per share in value creation, according to HOLT. If instead of an all-cash deal, PFE issues shares to pay for a portion, dilution from issuing “undervalued” shares will offset the initial value creation. A deal partially financed with an 18% stock issuance would be a break-even for PFE shareholders.
Shares of Bristol-Myers Squibb have fallen 0.68% to $55.89, while Pfizer has fallen 0.74% to $34. Novartis has gained 0.73% to $74.37, and Gilead Sciences has declined 0.76% to $67.51.
___________________________________________
http://blogs.barrons.com/stockstowatchtoday/2017/03/27/bristol-myers-maybe-a-pfizer-acquisition-could-makes-sense-after-all/
BMY
Out GIII @ $22.80 for a small loss after averaging down. Didn't want to be in when the quarterly is released on Mon, especially with the volatility of the health care repeal defeat. Could go up (has been strange bidding up after close), but has been down ~20% on several of the last reports. Willing to take my loss.
GIII
Bristol-Myers Squibb Receives Positive CHMP Opinion Recommending Opdivo (nivolumab) for the Treatment of Squamous Cell Cancer of the Head and Neck in Adults Progressing on or After Platinum-based Therapy
By Business Wire, March 24, 2017, 08:31:00 AM EDT
First Immuno-Oncology agent to receive positive CHMP opinion for the treatment of an advanced form of head and neck cancer
Positive opinion based on overall survival benefit demonstrated in the Phase 3 CheckMate -141 trial
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY) today announced that the Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Opdivo as monotherapy for the treatment of squamous cell cancer of the head and neck (SCCHN) in adults progressing on or after platinum-based therapy. This CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). This is the first CHMP positive opinion to recommend a PD-1 inhibitor for this type of treatment for SCCHN. Opdivo is already approved by the EC for six indications in four distinct tumor types.
"Nearly half of all patients with squamous cell cancer of the head and neck relapse within two years of treatment and limited advancements have been made in the last 10 years, underscoring the critical need for new treatment options for patients affected by this devastating illness," commented Emmanuel Blin, senior vice president and chief strategy officer, Bristol-Myers Squibb. "We are very pleased that the CHMP has recommended the approval of Opdivo for adults with squamous cell cancer of the head and neck who have progressed on or after platinum-based therapy and look forward to working with the EC as they review this treatment as a potential option for patients in the EU."
The CHMP adopted a positive opinion based on results from CheckMate -141, a pivotal Phase 3 open-label, randomized trial, that evaluated the overall survival (OS) of Opdivo in previously treated patients with SCCHN following platinum-based therapy compared to investigator's choice of therapy (methotrexate, docetaxel, or cetuximab) in the adjuvant, primary, recurrent or metastatic setting. Based on a planned interim analysis, this trial was stopped early in January 2016 because an assessment conducted by the independent Data Monitoring Committee concluded the study met its primary endpoint of OS superiority in patients receiving Opdivo compared to investigator's choice of therapy. Overall survival data from CheckMate -141 were first presented at the 2016 Annual Meeting of the American Association for Cancer Research. The safety profile of Opdivo in CheckMate -141 was consistent with prior studies in other tumors.
About Head & Neck Cancer
Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, the nose and the throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease. Squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 90% of all head and neck cancers with global incidence expected to increase by 17% between 2012 and 2022. Risk factors for SCCHN include tobacco and alcohol consumption. The Human Papilloma Virus (HPV) infection is also a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America. Quality of life is often impacted for SCCHN patients, as physiological function (breathing, swallowing, eating, drinking), personal characteristics (appearance, speaking, voice), sensory function (smell and hearing), and psychological/social function can be affected.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo's leading global development program is based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
U. S. FDA APPROVED INDICATIONS FOR OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.
In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator's choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%).
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).
Checkmate Trials and Patient Populations
Checkmate 067 - advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 - advanced melanoma; Checkmate 017 - squamous non-small cell lung cancer (NSCLC); Checkmate 057 - non-squamous NSCLC; Checkmate 025 - renal cell carcinoma; Checkmate 205/039 - classical Hodgkin lymphoma; Checkmate 141 - squamous cell carcinoma of the head and neck; Checkmate 275 - urothelial carcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies - as single agents and combination regimens - for patients with cancer in Japan, South Korea and Taiwan.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Opdivo will receive regulatory approval in the European Union for an additional indication. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170324005305/en/
Source: Bristol-Myers Squibb Company
Read more: http://www.nasdaq.com/press-release/bristolmyers-squibb-receives-positive-chmp-opinion-recommending-opdivo-nivolumab-for-the-treatment-20170324-00320#ixzz4cFMyEtVe
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BMY
Sold for now @ $14.00. Saw overall market dip following breakdown of healthcare talks and was unsure how Libbey would respond.
Will be back. Stock pps sure moves very slow throughout a day.
LBY
No one in LBY? In @ $13.55 when dropped at the end of day. Never traded it, but piqued my interest when saw this:
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Stocks to Buy Before They Join This Market Rally: Libbey (LBY)
Stocks to Buy Before They Join This Market Rally: Libbey (LBY)YTD Performance: -27%
Like FMSA, Libbey Inc. (NYSE:LBY) had a rough fourth quarter report in February, with the stock declining 17% after missing analyst estimates badly. The company’s glassware products — sold to both consumers and restaurants — have struggled with demand, and a work stoppage in Ohio further pressured Q4 earnings.
But shares have stabilized since the decline, rising steadily off a four-year low hit in early March. Libbey continues to hold dominant share and drive double-digit EBITDA margins. The company’s 2017 guidance was somewhat disappointing, but even with efficiency investments, profits should be relatively flat year-over-year.
There are short-term challenges, but the long-term case still holds for a company set to celebrate its 200th anniversary next year. An improving economy should boost demand, both from household formation and increased restaurant visits (and glass breakage). A 3.3% dividend yield adds income to the bull case as well.
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http://investorplace.com/2017/03/10-clobbered-stocks-to-buy-red-hot/5/#.WNJtofnytPY
Hopefully near bottom:
The ATM expires at the end of this month and there may be shares to be exercised:
"On April 1, 2016, we entered into an ATM sales agreement under which we are able, at our discretion and from time to time, to sell up to 3 million of our common shares through ATM issuances on the NASDAQ for aggregate gross proceeds of up to approximately $10 million. The ATM program provides that common shares are to be sold at market prices prevailing at the time of sale and, as a result, prices may vary. Subsequent to December 31, 2016 , the Company issued an additional 555,068 common shares under the April 2016 ATM Program at an average price of approximately $3.20 per share for gross proceeds of approximately $1.8 million. The shelf registration statement pursuant to which this program was established expires on March 28, 2017."
From Form 20-F
AEZS
Most detailed and accurate information regarding AEZS (filed on March 16, 2017):
http://secfilings.nasdaq.com/filingFrameset.asp?FilingID=11934855&RcvdDate=3/16/2017&CoName=AETERNA%20ZENTARIS%20INC.&FormType=20-F&View=html
AEZS
Bristol-Myers Squibb and Pfizer Present Large Real-World Observational Analysis of the Effectiveness and Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients with Non-Valvular Atrial Fibrillation
By Business Wire, March 17, 2017, 11:15:00 AM EDT
In this U.S. Medicare database analysis, Eliquis® (apixaban) was associated with significantly lower risk of stroke or systemic embolism and lower rate of major bleeding compared to warfarin
PRINCETON, N.J. & NEW YORK--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY) and Pfizer Inc. (NYSE:PFE) today announced findings from a real-world data analysis of the U.S. Medicare database comparing the risk of stroke or systemic embolism and rate of major bleeding among patients with non-valvular atrial fibrillation who were treated with direct oral anticoagulants versus warfarin. In the analysis, titled Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Compared to Warfarin among Non-Valvular Atrial Fibrillation Patients in the U.S. Medicare Population, Eliquis® (apixaban) was associated with a significantly lower risk of stroke or systemic embolism and lower rate of major bleeding compared to warfarin.i These data, which supplement results from randomized trials, are being presented at the American College of Cardiology's (ACC) 66th Annual Scientific Session in Washington, D.C.
In this observational analysis, medical and pharmacy claims were evaluated from the U.S. Medicare fee-for-service database of non-valvular atrial fibrillation patients age 65 and older who were newly prescribed oral anticoagulation therapy between January 1, 2013, and December 31, 2014 (n=186,132, following inclusion and exclusion criteria). The analysis included 41,606 patients treated with Eliquis or warfarin (20,803 patients each in the Eliquis and warfarin cohorts), balanced according to select demographic and clinical characteristics. The matched Eliquis-warfarin cohorts, followed for a mean of 5.7 and 6.5 months, respectively, had a mean age of 78 years, a CHA2DS2-VASc score of 4.6 and 4.7, respectively, and a HAS-BLED score of 3.3. CHA2DS2-VASc score is a method for estimating stroke risk in patients with atrial fibrillation, and HAS-BLED score helps to estimate risk of major bleeding in patients with atrial fibrillation. Real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. Observational real-world studies can only evaluate association and not causality.ii,iii Please see full methodology and additional limitations below.
"Studies such as this large U.S. Medicare database analysis supplement pivotal trials by broadening and deepening our scientific knowledge of how patients respond to direct oral anticoagulants in everyday clinical practice," said Alpesh Amin, M.D., principal investigator and Professor of Medicine, University of California, Irvine. "Given the diversity of patients with non-valvular atrial fibrillation, analyses of real-world data provide further information that adds to data generated in randomized clinical trials."
Eliquis, in this analysis, was associated with a significantly lower risk of stroke or systemic embolism (HR: 0.40, 95% CI: 0.31-0.53; p<0.0001) and lower rate of major bleeding (HR: 0.51, 95% CI: 0.44-0.58; p<0.0001) than patients treated with warfarin. The findings from the Eliquis-warfarin cohort complement the results of the randomized Phase 3 ARISTOTLE (Apixaban for Reduction In Stroke and Other ThromboemboLic Events in Atrial Fibrillation) trial.iv For data on other cohorts, please refer to the full abstract.
"The U.S. Medicare system currently covers more than 57 million Americans,v including over two million who have been treated with anticoagulants," said Rory O'Connor, M.D., Chief Medical Officer, Pfizer Innovative Health. "Increasingly, real-world data analyses are being utilized to enhance the understanding of data associated with health interventions. With the advent of large, representative and anonymized datasets, such as records from the Centers for Medicare & Medicaid Services, we can provide additional information that clinicians can use in their treatment decisions."
"The Bristol-Myers Squibb and Pfizer Alliance continues to invest heavily in research analyses that provide more information on care for patients with non-valvular atrial fibrillation," said Christoph Koenen, M.D., MBA, VP, Development Lead, Eliquis, Bristol-Myers Squibb. "Our real-world data program - ACROPOLIS™ - aims to generate evidence from routine clinical practice settings by analyzing patient databases around the world, including medical records, medical and pharmacy health insurance claims data and national health data systems."
Methodology
In addition to the apixaban cohort, this analysis of the U.S. Medicare database included cohorts comparing two other direct oral anticoagulants (rivaroxaban and dabigatran) separately with warfarin. The analysis was conducted in patients age 65 and older with non-valvular atrial fibrillation who had not received an oral anticoagulant for at least one year. Patients had to have continuous health plan enrollment with medical and pharmacy benefits for at least 12 months pre-index date. Patients with evidence of valvular heart disease, transient atrial fibrillation, venous thromboembolism, valve replacement or surgery or indication of pregnancy 12 months prior to the index date were excluded.
This analysis was designed according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines for comparative effectiveness research, which include recommendations for research question development, transparency of analytical plans and control of confounding factors.vi,vii,viii One-to-one propensity score matching methodology (PSM) was applied in the analysis to balance select demographic and clinical characteristics. Cox proportional hazards models were used to estimate the hazard ratio (HR) of stroke/systemic embolism and major bleeding using primary ICD-9 codes of inpatient claims.
Limitations of Real-World Data Analyses and of the U.S. Medicare Database Analysis
Real-world data have the potential to supplement randomized clinical trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses have several limitations. For example, the source and type of data used may limit the generalizability of the results and of the endpoints. It is important to note that there are no head-to-head clinical trials comparing direct oral anticoagulants.
In the U.S. Medicare database analysis, laboratory results and time in therapeutic range information were not available. Diagnoses were identified through ICD-9 codes, and drug prescriptions were identified through prescription claims. PSM methodology was used to mimic randomization by balancing pre-defined demographic and clinical characteristics at baseline for both treatment cohorts. As an observational study using PSM, unobserved cofounders (e.g., laboratory values and patient preferences) may exist for which the analysis did not control. As with any real-world data analysis, missing values, coding errors and lack of clinical accuracy may have introduced bias.
Due to these limitations, real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. Observational real-world studies can only evaluate association and not causality.ii,iii
About Eliquis
Eliquis (apixaban) is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation and blood clot formation. Eliquis is approved for multiple indications in the U.S. based on efficacy and safety data from seven Phase 3 clinical trials. Eliquis is a prescription medicineindicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF); for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE, following initial therapy.
ELIQUIS Important Safety Information
WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA
(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:
use of indwelling epidural catheters
concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
a history of traumatic or repeated epidural or spinal punctures
a history of spinal deformity or spinal surgery
optimal timing between the administration of ELIQUIS and neuraxial procedures is not known
Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.
CONTRAINDICATIONS
Active pathological bleeding
Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)
WARNINGS AND PRECAUTIONS
Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding.
Concomitant use of drugs affecting hemostasis increases the risk of bleeding, including aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs.
Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available.
Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis.
The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours.
Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients.
Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients.
Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.
ADVERSE REACTIONS
The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding.
TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS
ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.
DRUG INTERACTIONS
Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when ELIQUIS is coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with strong dual inhibitors of CYP3A4 and P-gp.
Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) because such drugs will decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events.
Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.
PREGNANCY CATEGORY B
There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.
Please see full Prescribing Information, including BOXED WARNINGS and Medication Guide, available at www.bms.com.
About ACROPOLIS™
ACROPOLIS™ (Apixaban ExperienCe Through Real-WOrld POpuLatIon Studies) is the Eliquis (apixaban) global real-world data program designed to generate additional evidence from routine clinical practice settings to further inform healthcare decision makers, including healthcare providers and payers. The ACROPOLIS program will include retrospective, outcomes-based analyses from over 10 databases around the world, including medical records, medical and pharmacy health insurance claims data, and national health data systems.
Analyses of real-world data allow for a broader understanding of patient outcomes associated with Eliquis outside of the clinical trial setting, as well as insight into other measures of healthcare delivery, such as hospitalization and costs.
About ARISTOTLE
ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) was designed to evaluate the efficacy and safety of Eliquis versus warfarin for the prevention of stroke or systemic embolism. In ARISTOTLE, 18,201 patients were randomized (9,120 patients to Eliquis and 9,081 to warfarin). ARISTOTLE was an active-controlled, randomized, double-blind, multi-national trial in patients with nonvalvular atrial fibrillation or atrial flutter, and at least one additional risk factor for stroke. Patients were randomized to treatment with Eliquis 5 mg orally twice daily (or 2.5 mg twice daily in selected patients, representing 4.7 percent of all patients) or warfarin (target INR range 2.0-3.0), and followed for a median of 1.8 years.
About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize apixaban, an oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug development and commercialization with Pfizer's global scale and expertise in this field.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
About Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @PfizerNews, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Pfizer Disclosure Notice
The information contained in this release is as of March 17, 2017. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Eliquis (apixaban), including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including, without limitation, the ability to meet anticipated clinical trial commencement and completion dates as well as the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of Eliquis; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2016 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the SEC and available at www.sec.gov and www.pfizer.com.
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i Amin A, Keshishian A, Trocio J, et al. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban compared to warfarin among non-valvular atrial fibrillation patients in the US Medicare population. Presented at the 66th Annual American College of Cardiology (ACC) Scientific Session; March 17, 2017; Washington, D.C.
ii Garrison LP, Neumann PJ, Erickson P, Marshall D, Mullins CD. Using real-world data for coverage and payment decisions: the ISPOR real-world data task force report. Value Health. 2007;10:326-335.
iii Hannan EL. Randomized clinical trials and observational studies. J Am Coll Cardiol Intv. 2008;1:211-217.
iv Granger, CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.
v Centers for Medicare & Medicaid Services. Medicare Enrollment Dashboard. Accessed March 7, 2016. Available at https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Dashboard/Medicare-Enrollment/Enrollment%20Dashboard.html.
vi Berger ML, Mamdani M, Atkins D, Johnson ML. Good Research Practices for Comparative Effectiveness Research: Defining, Reporting and Interpreting Nonrandomized Studies of Treatment Effects Using Secondary Data Sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report—Part I. Value in Health. 2009:12(8):1044-1052.
vii Cox E, Martin BC, Van Staa T, et al. Good Research Practices for Comparative Effectiveness Research: Approaches to Mitigate Bias and Confounding in the Design of Nonrandomized Studies of Treatment Effects Using Secondary Data Sources: The International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report—Part II. Value in Health. 2009:12(8):1053-1061.
viii Johnson ML, Crown W, Martin BC, Dormuth CR, Siebert U. Good Research Practices for Comparative Effectiveness Research: Analytic Methods to Improve Causal Inference from Nonrandomized Studies of Treatment Effects Using Secondary Data Sources: The ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report—Part III. Value in Health. 2009:12(8):1062-1073.
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Source: Bristol-Myers Squibb and Pfizer
Read more: http://www.nasdaq.com/press-release/bristolmyers-squibb-and-pfizer-present-large-realworld-observational-analysis-of-the-effectiveness-20170317-00548#ixzz4bb7rQtj4
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BMY
Aeterna Zentaris' (AEZS) CEO David Dodd on Q4 2016 Results - Earnings Call Transcript
Mar. 16, 2017 4:07 PM ET| About: AEterna Zentaris, Inc. (AEZS)
Q4: 03-15-17 Earnings Summary
Slides News
EPS of $-0.71 beats by $0.02 | Revenue of $0.3M (+ 200.0% Y/Y) misses by $-0.1M
Aeterna Zentaris, Inc. (NASDAQ:AEZS)
Q4 2016 Earnings Conference Call
March 16, 2016 8:30 AM ET
Executives
Philip Theodore - Senior Vice President, Chief Administrative Officer, General Counsel and Corporate Secretary
David Dodd - President and Chief Executive Officer
Genevieve Lemaire - Vice President, Finance and Chief Accounting Officer
Analysts
Jason Kolbert - Maxim Group, LLC
Swayampakula Ramakanth - H.C. Wainwright & Co.
Operator
Greetings and welcome to the Aeterna Zentaris Fourth Quarter and Full-Year 2016 Financial and Operating Results Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded.
It is now my pleasure to introduce your host, Philip Theodore, for Aeterna Zentaris. Thank you, Mr. Theodore. You may now begin.
Philip Theodore
Good morning and welcome, everyone. I'm Philip A. Theodore, Senior Vice President and General Counsel of Aeterna Zentaris. And I'm the leader of today's call. With me are David Dodd, President and CEO; and Genevieve Lemaire, Vice President Finance and Chief Accounting Officer.
During this call, we will be making forward-looking statements regarding future events and the performance of Aeterna Zentaris. The forward-looking statements are subject to risks and uncertainties that could cause actual events and results to differ materially from the forward-looking statements. These risks are described in further detail in the company's press releases and reports filed with the U.S. and Canadian securities regulatory authorities.
These forward-looking statements represent the company's judgment as of today, Thursday, March 16, 2017 and the company disclaims any intent or obligation to update these forward-looking statements unless required to do so by applicable law or by a securities regulatory authority. However, we may choose to update the forward-looking statements, and if we do so, we will disseminate the updates to the investing public.
It is now my pleasure to introduce the President and CEO of Aeterna Zentaris, Mr. David Dodd. David?
David Dodd
Thank you. Good morning. Thank you for joining us. As we await for the news regarding our development projects, we are focused on our capital structure and are making sure that we have sufficient capital to see our potential products through to commercialization, if one or both of them receives approval. We ended the year with approximately $22 million of unrestricted cash and cash equivalents, which is indicative of an average monthly use of cash in operations of approximately $2.4 million during 2016, representing a year-over-year reduction of almost 15% in our monthly use of cash in operations.
At the end of the year, we had approximately 12.9 million common shares outstanding. During the first quarter of 2017 to date, we raised an additional $1.7 million of net proceeds using our ATM program. And we now have approximately 13.5 million common shares outstanding.
After year-end, we reported top line results from our confirmatory Phase 3 study of Macrilen for the evaluation of Adult Growth Hormone Deficiency or AGHD. We were disappointed by the top line results as we failed to meet one of the co-primary endpoints of the study.
However, our disappointment soon gave way to optimism, as we evaluated the full data from the clinical trial. We concluded together with our panel of independent experts that Macrilen works even better than we had expected. And that it demonstrated performance that we believe is supportive of achieving registration with the U.S. Food and Drug Administration.
We will discuss the results of the clinical trial in our conclusions with the FDA at the end of March. And hope to have a timely decision regarding the future of the development of this drug. If the FDA agrees with us, we expect to be able to file the NDA or new drug application early third quarter, and if it is approved begin commercializing the product in first quarter of 2018.
As you may recall, the Macrilen confirmatory study consisted of two-way crossover comparison of Macrilen with the Insulin Tolerance Test or ITT. There were four patient cohorts evaluated in the trial, high risk, intermediate risk, low risk and healthy volunteers. The co-primary end points consisted of percent negative agreement and percent positive agreement, representing the percent agreement of Macrilen with the ITT results, when the ITT indicated that the patent either did not have or did have growth hormone deficiency.
For example, the percent negative agreement reflects the percent of Macrilen results that agreed with the ITT, when the ITT indicated that a patient was not deficient in growth hormone secretion. In other words, this would reflect a situation where a patient had a normal functioning pituitary gland.
Such a situation was determined by the FDA to represent the more critical comparison, since one would want to avoid diagnosing a patient as deficient and thereby prescribing growth hormone supplementation, when it isn't indicated. The criterion for achieving success relative to percent negative agreement was therefore established at a higher level than that for the percent positive agreement endpoint.
In addition, the trial included the evaluation of a subset of patients to determine the reproducibility of Macrilen results, since it is generally recognized that the reproducibility of ITT results is poor. This continuation study was requested by the European Medicines Agency or EMA to gain insight relative to the overall potential value of Macrilen for the diagnosis of suspected adult growth hormone deficient patients.
As we reported on January 4, we achieved one of the two co-primary endpoints, the percent negative agreement. Our results were impressive, reflecting a 94% agreement with the ITT. Unfortunately, we missed the percent positive agreement endpoint, demonstrating 74% agreement with the lower 95% confidence interval below that of the pre-established criteria.
However, further examination of the data provided confidence in the utility of Macrilen. And we are now scheduled to review these results in detail with the FDA by the end of March.
We believe that the Macrilen results demonstrate that the drug is not only supportive of registration, but that it provides more consistent, robust and reproducible results than the ITT. Our goal is to achieve concurrence with the FDA, so that we may proceed to a formal NDA submission in the near future.
Let me now briefly review the conclusions that we've reached and that we shared with the FDA. Macrilen stimulates pituitary gland effectively to secrete growth hormone. In fact, the stimulation was consistently more pronounced than that achieved with the ITT. Macrilen performed very well in the study, demonstrating sensitivity of 87% and specificity of 96%. This was even better than demonstrated in the previous study.
In the reproducibility extension portion of the study, Macrilen demonstrated 94% reproducibility, while reproducibility of the ITT was not investigated in the study it is known to demonstrate poor reproducibility.
Study results can be further optimized by modulation of the predefined Macrilen cut-off point of 2.8 nanograms per milliliter. In fact, any cut-off point for Macrilen between 4.6 nanograms per milliliter and 8.2 nanograms per milliliter would have resulted in a fully positive study outcome, meaning that both co-primary endpoints would have been met.
Macrilen was found to be a more robust test than the ITT, only one out of 153 Macrilen tests needed to be repeated compared to 28 out of 157 for the ITT. Finally, Macrilen's stimulation to growth hormone release was more pronounced and consistent than the ITT. In approximately 80% of all cases, peak growth hormone levels following administration of Macrilen were equal to or higher than those observed during the ITT. And this was consistent across each of the four cohorts evaluated.
Following our review of these results, we announced our conclusions and we shared the results with the FDA. We were pleased that the FDA so quickly agreed to meet with us within 30 days to review the data and to discuss appropriate next steps. Our hope is that the FDA will agree that the data support submission and review of the NDA for Macrilen.
We are also pleased to have reported that the EMA has formally issued their concurrence with our proposed pediatric investigational plan, which provides us the ability to pursue EMA registration in conjunction with our U.S. registration plan.
Shifting now to Zoptrex. On January 30, we announced the conclusion of the clinical phase of our development program for that product. The following day we had a successful pre-NDA meeting with the FDA. Based on the meeting we are now continuing to prepare our NDA for the product and we now expect to report top-line results before the end of April. If the results were supportive we anticipate submitting the NDA in third quarter.
Now, I will turn the call over to Genevieve Lemaire, our Vice President, Finance, and Chief Accounting Officer, who will provide more information about our fourth quarter and year-end financial results.
Genevieve Lemaire
Thank you, David, and good morning, everyone. Most of what I'll be covering has been presented in more detail in our consolidated financial statement and MD&A for the fourth quarter and year-end, which were filled yesterday.
From an operating expense standpoint, our main operating activities during the fourth quarter included ongoing efforts associated with our clinical development initiatives as well as to a lesser extent with our commercial operation, and general and administrative activity.
Total operating expenses amounted to approximately $7.9 million for the quarter ended December 31, 2016, representing a 21% decrease compared to the same period in 2015. The decrease is mainly explained by the movement in G&A expenses, which will be discussed in the following slides.
Our total R&D costs in the quarter were approximately $4.6 million as compared to approximately $4.2 million in the fourth quarter of 2015. The increase in R&D expenses of approximately $400,000 is mainly attributable to higher comparative third-party costs in connection with the confirmatory Phase 3 clinical trial of Macrilen, which was initiated late in 2015 with the enrollment of the first patient in the fourth quarter of that year. And patient recruitment in the trial were completed in the fourth quarter of 2016.
R&D costs incurred in the fourth quarter of 2016 were lower than anticipated, mainly because we were able to negotiate reduction to a change order received from our principal R&D third-party service provider. Excluding the impact of foreign exchange rate fluctuation, we expect that we will incur overall R&D cost of between $19 million and $20 million for the year ending December 31, 2017.
Although we expect a decrease in costs related to the contract research organization following the end of the clinical trial, this will be offset by the costs associated with the NDA preparation for both products, the FDA submission fee for Zoptrex if the results of the clinical trial warrant submitting a new drug application, as well as by the investment needed in inventory prior to the potential commercial launch of both Macrilen and Zoptrex. In addition, we expect to incur costs related to the validation of a second supplier for both products to be able to fulfill the expected demand.
Switching now to our G&A expenses, during the quarter ended December 31, 2016, G&A expenses totaled approximately $1.8 million as compared to $4 million during the same period in 2015. The $2.2 million quarter-over-quarter reduction in G&A is mainly due to the recording in the fourth quarter of 2015 of a provision related to the restructuring of our finance and accounting functions, and the closing of our office in Quebec City, as well as the realization of cost savings from the restructuring.
The comparative decrease is also explained by the allocation of certain transaction costs to the warrant we issued in connection with our equity offering in December 2015. Excluding the impact of foreign exchange rate fluctuation and the recording of transaction costs related to potential financing activity which are not currently known or estimate of, we expect G&A expenses to slightly increase in 2017 as compared to 2016, because we expect to hire additional employees necessary for the potential commercialization of our products.
We expect that G&A expenses will range between $7.5 million and $8.5 million in 2017 as compared to $7.1 million in 2016. From a commercial operation standpoint, we continue during the fourth quarter to incur costs related to our contract sales force and our own management staff in support of our co-promotion agreement for Saizen and APIFINY.
Selling expenses during the fourth quarter of 2016 were approximately $1.5 million and were essentially unchanged compared to the selling expenses during the same period in 2015.
Selling expenses are slightly below what we anticipated, because we put down some expenses related to the potential commercial launch of Zoptrex and Macrilen, mainly because of related clinical trials took more time than expected.
Based on currently available information, we expect selling expense to range between $7 million and $8 million in 2017. The expected increase in 2017 as compared to 2016 is mainly because we are preparing for the expected commercial launch of Zoptrex and Macrilen.
We reported net finance costs of approximately $0.6 million in the fourth quarter of 2016 as compared to net finance costs of approximately $0.2 million during the fourth quarter of 2015. The variance is mainly attributable to the change in fair value of our warrant liability, which resulted from the periodic mark-to-market valuation of our outstanding warrants.
The mark-to-market warrant valuation during the quarter was mainly impacted by a closing price of our common share on the NASDAQ, which was more stable in the fourth quarter of 2016 as compared to the same period in 2015. In addition, with specific reference to the fourth quarter of 2016, finance costs were also impacted by the warrant exercise inducement fee paid to certain holders of the Series B Warrants.
From a cash flow standpoint, we use approximately $8.1 million of cash in operation in the fourth quarter of 2016 as compared to approximately $8.4 million in the same period in 2015. We used less cash in the fourth quarter of 2016 than in the prior year quarter primarily because of lower operating expenses.
During the year ended December 31, 2016, our average monthly cash used in operation was approximately $2.4 million, representing a year-over-year reduction of almost 15% in our monthly use of cash in operation.
Cash used in operation was lower than initially anticipated, because we incurred less R&D costs as explained in the previous slide. We expect net cash used in operating activities to range from $30 million to $32 million for the year ending December 31, 2017, as we finalize our Zoptrex Phase 3 program as well as prepare for Zoptrex and Macrilen NDA submission and commercial launch, and as we expect to generate higher revenues in connection with the promotion of Saizen and APIFINY.
This guidance may vary significantly in future periods, as it assumes that Zoptrex Phase 3 study will be positive and that we will be able to register Macrilen.
We also expect net cash used in investing activity to range from $1 million to $1.5 million for the year ending December 31, 2017, as we must invest in IT as well as in manufacturing capacity, while we are preparing for the potential commercial launch of Macrilen and Zoptrex. We ended the year with unrestricted cash and cash equivalents of approximately $22 million.
And now, I'll turn the call back over to David, who will entertain questions.
David Dodd
Thank you, Genevieve. We will now entertain your questions. I'm therefore turning the call over to operator for instructions on the question-and-answer period.
Question-and-Answer Session
Operator
Thank you. We will now be conducting a question-and-answer session. [Operator Instructions] Our first question comes from the line of Jason Kolbert with Maxim. Please proceed with your question.
Jason Kolbert
Good morning, guys, and congratulations on all the progress. Two questions. One, very pleased to understand that Macrilen is coming back. Can you give us a little bit of the more details or granularity on your - the discussions that you've already had with regulators that led you do this optimistic point of view?
And then second question, obviously very excited on Zoptrex, can you help me understand, when you look at the data and the time to events that have occurred, how that compares to what would be expected versus standard of care, meaning that it took a little bit longer to get the time to event suggesting that there is maybe some additional efficacy associated with Zoptrex? Thank you.
David Dodd
Thanks, Jason. This is David. Regarding Macrilen, we have had no discussions with regulators related to the data analysis other than submitting to them our conclusions and then a briefing document, which they have for their review in advance of our meeting, which is scheduled for the end of March. So to date, following the January 4 and then the subsequent analysis that we and our external experts have conducted, we reached the conclusions which we announced on February 13.
We have supplied the information that is the basis of that analysis, and that analysis to the FDA and we requested a meeting. And they responded to have a meeting within 30 days of our request. So that's really where we are at this stage.
So the process includes as it does for any such meeting between a client and our company and the regulators is when they agree to it depending on the type of meeting et cetera, one will submit a briefing document. In this case, we did that and we sent that in and they have that. And they will be reviewing it and then our team will meet with them. And then following that, and following the decisions come out that we will announce accordingly.
Regarding Zoptrex, certainly as we have announced over the - generally past year, the closing of the trial was long - it took longer than what we had originally anticipated, that original anticipation was generated when we started talking about it based upon initially just general assumptions and then what we were observing as the rate of events on a monthly basis.
And one might - you may recall, I previously noted that in January of 2016 we were receiving between 20 and 25 events per month. And then we saw it go down to as low as 3 to 5 per month, and that resulted in it taking longer to get to the requisite minimum number of 384 events in all.
Now, given that the data that is published out in the marketplace is not current data, it's historical data, studies are historical, we caution ourselves and others on trying to overly interpret what this timing means. Clearly, it means that for many individuals that there were patients that seem to be surviving and living longer than what one might have anticipated based on a knowledge of survival of women in this situation now.
However, recall that the protocol of having half the patients on Zoptrex and half the patients on doxorubicin and half the patients on doxorubicin, it excludes any other anthracyclines. But it certainly allows their oncologist, their physician to provide what they feel as the best care for the patients. And over the last several years, we've seen new therapies come into the marketplace, perhaps not for specific related indication, but as we all know in oncology it is not uncommon for an oncologist to utilize of whatever tools they feel might benefit that particular patient.
And so, it would be wrong for people to think that in the study that 512 patients, half were only on Zoptrex and half were only on doxorubicin, half were randomized to receive Zoptrex, the other half doxorubicin. But that was in addition to whatever care their oncologist was providing. And so, ultimately, as much as we would like to try and interpret what might be going on, we'll just have to wait until the end of April to see to the extent that there is a difference in the median overall survival between the two treatment arms and all.
But I do want to point out that the process and the trial was not as some people have asked me before, not yourself, but others have, so half were only on Zoptrex and half were only on doxorubicin. That is incorrect, because half - because all of them are managed by well-attended physicians. And they're going to do the best job they can, but they will follow the protocol not to incorporate any other anthracyclines into the trial.
Jason Kolbert
David, thank you very much for the comprehensive answer. We really look forward to seeing the data.
David Dodd
Thank you. Thank you. Hope that useful.
Operator
[Operator Instructions] Our next question comes from the line of RK with H.C. Wainwright & Co. Please proceed with your question.
Swayampakula Ramakanth
Thank you. Good morning, David.
David Dodd
Thanks.
Swayampakula Ramakanth
Congratulations on the progress so far and on both the programs. In terms of expectations for the Zoptrex data in late April, what sort of data can we see in the initial announcement, which you're going to put out in late April?
David Dodd
Excellent question, RK. I was actually just thinking I was going to work that into an answer, whatever you asked. So what we will be - what will be include in the top-line results information that we will receive will certainly include the primary endpoint of median overall survival between Zoptrex and doxorubicin. However, we have also incorporated so that at that time we will also have received information on secondary endpoint, such as progression free survival, et cetera.
We've also been able to incorporate into what we are requesting as part of the top-line results package, let's call it data package will include some side-effect data. Previously, I had stated on such calls and in various settings that we did not anticipate to receive any side-effect data as part of the top-line results, but in fact we have requested such, and that's why we discuss by the end of April rather than in an earlier time period.
Obviously, it takes more time, but we believe it would be more meaningful and certainly beneficial to have more data rather than less data that we are able to discuss.
Everyone will be focused on the primary endpoints. We understand that. But people will want to then know regardless on the secondary endpoints and also side-effects. So we anticipate having a packet of information that we will be able to discuss and disclose.
Swayampakula Ramakanth
Thank you. Thank you for that. In the - in pre-NDA meeting that you had with the FDA, which was right after closing the study, what sort of topics were discussed in that meeting, because obviously I don't think data was there? So I was wondering what could you tell the FDA, how that FDA come to the conclusion that was regarding your application for approval?
David Dodd
Could you restate your question? It broke up a little bit, RK, I apologize, I didn't catch. Which meeting are you referencing?
Swayampakula Ramakanth
The pre-NDA meeting on…
David Dodd
Oh, yes, I'm sorry. I understand. The pre-NDA meeting, which we had on January 31, that is a - it is a meeting that a company anticipating to be submitting, plans to submit a NDA will have. In advance of the meeting, we provided a briefing document, which contained our questions. We had 10 questions we asked of them. And they were all about ensuring that we and the FDA were in agreement on what is expected to be included in the FDA - or, excuse me, in the NDA submission, what types of data there.
And we also had some questions that we were seeking clarification from them that will be relevant, should we be successful and be proceeding towards what we would anticipate and be hopeful of a registration on. So in any pre-NDA meeting, it usually addresses the core elements so that the client of the FDA fully understands what is going to be expected. Remember, this study was conducted on a special protocol assessment. So that was the basis of discussion, because the protocol was agreed to et cetera.
But there are always elements perhaps about certain associated data, certain data that may come from related to standard doxorubicin should it be included, would it be of interest, all of those types of things would be necessary. So that's really what it was.
We submitted by the end of December our document. We had the meeting a month later. In the interim, they had reviewed everything. In fact, they had actually already responded and agreed to all of our questions. But we still had the meeting. That we felt it would be a - it would be beneficial to both parties to have face-to-face meeting. So our team met with them and addressed everything. And that was very useful for us.
Swayampakula Ramakanth
Okay. And then the next question is on Macrilen. So you're going and meeting with the FDA at the end of first quarter regarding your next study with Macrilen. So if FDA gives you the green signal on the next study, can you help us understand the timeline for the start of the study and how long the study could take and when the data would come?
David Dodd
Well, first of all, our focus and our hope is that there is no - we're going in there with a - our proposal is that the current existing data coming out of the study that we reported on January 4 is sufficient and supportive for them to accept for review a potential approval of Macrilen.
Swayampakula Ramakanth
Okay.
David Dodd
That is what we are requesting for their answer on. And we anticipate there could be three main answers. One could be, yes, we agree. And if that's the case, then we would proceed towards a submission, which we would believe in early Q3, and would allow us to be commercializing the product if it's approved in early next year. They could say, we agree - with whatever, they can say whatever. They can say, they agree with all of our data, but they request us to validate it by conduct of another trial. That trial would not be the same trial, because we wouldn't have to repeat the reproducibility portion nor would we own the QT interval study portion of that.
That trial is what you're asking of, would take, we believe, approximately 18 months and cost approximately $1 million and all. So that's what would be involved in that. As you can imagine, when we have to get set up, you have to determine the protocol. You don't just go back to all the same sites and tell them, okay, crank it back up. I mean, you through - it's an entirely new program, that's why it's 18 months. The conduct of it would be about a year, but no matter how you approach it, it's going to be approximately 18 months now.
The third outcome that could occur would be that the FDA agrees with the basis of what that we've concluded and our experts have concluded, and they ask - and they agree to accept it for review and potential approval, but they could require us to conduct another trial while the product - Phase 4 commitment. So while the product is on the market.
And so, I think those are the three outcomes that could occur. And obviously our decision is that based on the data analysis and what we've seen and what others have seen, that the data is supportive for their acceptance as part a NDA dossier. And that's what we hope to. And we will be announcing, as we come out of that meeting and have their answer, we will announce, obviously, what they decide and what they tell us.
Swayampakula Ramakanth
Okay. Thank you. And then the last question for me is on the exclusivity that you have on the IP part for both Macrilen and Zoptrex, in terms of how much life is left on - in terms of IP for both of these drugs.
David Dodd
Sure, sure. Macrilen is patented. It's covered by patent to the end of 2027. It also has orphan drug status, which gives it the seven years exclusivity. So that's pretty nice for that product. You may recall Zoptrex, the composition of matter patent expired. I believe the last one expired in 2016. It will have five years formal exclusivity in the U.S., because it's part of a clinical trial supported 10 years in Europe.
We believe that that five year in the U.S. actually translates to seven to eight years, because of the time that is involved. And also recall that we are currently prosecuting a pattern on the manufacturing aspect of Zoptrex, which can be a very expensive drug to make. And we believe that this process has the - can reduce the manufacturing cost by half or more. So we believe we would have a strong competitive advantage to any potential generics. Bottom line is Zoptrex is not an inexpensive API to make.
Swayampakula Ramakanth
Okay, okay. Thank you. That's all I have. Good luck.
David Dodd
Thank you. Thank you.
Operator
Thank you. There are no further questions at this point. I would like to turn the call back over to Mr. David Dodd for closing remarks.
David Dodd
Thank you. And thank you everyone for your continued support and your interest in the transformation of Aeterna Zentaris. We look forward to updating you regarding further progress, when we discuss first quarter 2017 results. For now, thank you, and have a great day.
Operator
This concludes today's teleconference. You may now disconnect your lines at this time. Thank you for your participation. And have a wonderful day.
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AEZS
Aeterna Zentaris Reports Fourth Quarter and Full-Year 2016 Financial and Operating Results
By Business Wire, March 15, 2017, 04:48:00 PM EDT
Clinical phase of Zoptrex™ and Macrilen™ development programs completed; Zoptrex™ top-line results expected in April
All amounts are in US Dollars
Recent key developments
Development programs progressing toward completion
Zoptrex™ (zoptarelin doxorubicin) pivotal Phase 3 trial clinically completed on January 30, 2017; pre-NDA meeting with FDA held on January 31, 2017; top-line results expected to be reported in April 2017
Company believes that analysis of data from confirmatory Phase 3 trial of Macrilen™ (macimorelin) is supportive of registration consideration; Meeting with FDA will be held at the end of Q1
Financial condition and capital structure improved
$22.0 million unrestricted cash and cash equivalents at year-end; no third-party debt
Approximately $7.6 million of gross proceeds raised from a successful registered direct offering of Units concluded on November 1, 2016
Approximately $4.7 million of gross proceeds raised from sales of Common Shares pursuant to ATM program during and subsequent to the fourth quarter
Approximately 13.5 million Common Shares outstanding as of March 15, 2017
CHARLESTON, S.C.--(BUSINESS WIRE)--
Aeterna Zentaris Inc. (NASDAQ:AEZS) (TSX:AEZS) (the "Company"), a specialty biopharmaceutical company engaged in developing and commercializing novel treatments in oncology and endocrinology, today reported financial and operating results for the fourth quarter and year ended December 31, 2016.
Commenting on recent key developments, David A. Dodd, President and Chief Executive Officer of the Company, stated, "During the fourth quarter and the first few weeks of 2017, we made substantial progress with our development programs. On January 30, 2017, we announced the conclusion of the clinical phase of our development of Zoptrex™. The following day we had a successful pre-NDA meeting with the FDA. We anticipate reporting top-line results in April. This is a very exciting and anxious time for us, as we approach the culmination of highly dedicated and successful work by many throughout our Company. I would like to thank our R&D team for their hard work in bringing Zoptrex™ to this point."
Mr. Dodd continued his commentary with an update on the development of Macrilen™. "On January 4, 2017, we reported the top-line results from our confirmatory Phase 3 study of Macrilen™ for the evaluation of adult growth hormone deficiency ("AGHD"). We reported that the top-line results indicated that macimorelin did not meet one of the pre-defined criteria required to demonstrate equivalence to the Insulin Tolerance Test ("ITT") as a means of diagnosing AGHD. Following this announcement, we conducted a thorough evaluation of the study data, including external statistical expertise and independent review by leading endocrinologists in both the U.S. and Europe. We were highly encouraged by the results and input received from these experts. As we announced on February 13, 2017, we concluded that Macrilen™ demonstrated performance supportive of achieving registration with the U.S. Food and Drug Administration, despite its failure to meet one of the pre-defined equivalence criteria. We explained the reasons for our conclusion in our February 13 release. Briefly, we concluded that Macrilen™ demonstrated more consistent and reproducible results than the ITT. Moreover, Macrilen™ stimulated the pituitary gland more powerfully than the ITT and demonstrated good specificity and sensitivity in this study, thus reproducing the results of our previous study. We demonstrated that Macrilen™ achieves a high degree of correlation with the ITT, which could be further optimized when a higher cut-off point, such as the ITT cut-off point, is used for the Macrilen™ test. We believe that such an increased cut-off point would be justified by the more powerful stimulation of Macrilen™ as compared to the ITT. We are scheduled to meet with the FDA at the end of Q1 to discuss our rationale for proceeding with Macrilen™."
Fourth Quarter and Full Year Financial Highlights
Revenues
Sales commission and other were $94,000 and $414,000 for the three and twelve months ended December 31, 2016, respectively, and $41,000 and $297,000, for the same periods in 2015, respectively. The quarter-over-quarter and year-over-year increases were attributable to our sales team exceeding pre-established unit sales baseline thresholds under our co-promotion agreements to sell Saizen® and to our promotion of APIFINY®, which did not begin until the first quarter of 2016. In the corresponding periods of 2015, sales commission and other revenues were mainly related to EstroGel®, which we no longer promote.
License fees were $210,000 and $497,000 for the three and twelve months ended December 31, 2016, respectively, as compared to $61,000 and $248,000 for the same periods in 2015. The increase is explained by the out-licensing agreements that we entered into in 2016 for Zoptrex™ with respect to certain territories outside our core areas of interest.
Research and Development ("R&D") costs
R&D costs were $4.6 million and $16.5 million for the three and twelve months ended December 31, 2016, respectively, compared to $4.2 million and $17.2 million for the same periods in 2015. The increase in our R&D costs for the three months ended December 31, 2016, as compared to the same period in 2015, was mainly attributable to higher comparative third-party costs in connection with the confirmatory Phase 3 clinical trial of Macrilen™, which was initiated late in 2015 with the enrollment of the first patient in the fourth quarter of 2015. Patient recruitment was completed in the fourth quarter of 2016. The decrease in our R&D costs for the twelve months ended December 31, 2016, as compared to the same period in 2015, was mainly attributable to the realization of cost savings in connection with our ongoing efforts to streamline our R&D activities and to increase our commercial operations and flexibility by reducing our R&D staff, which was started in 2014.
General and Administrative ("G&A") Expenses
G&A expenses were $1.8 million and $7.1 million for the three and twelve months ended December 31, 2016, respectively, as compared to $4.0 million and $11.3 million for the same periods in 2015. The decrease in our G&A expenses for the three months and twelve months ended December 31, 2016, as compared to the same periods in 2015, is mainly due to the recording in the fourth quarter of 2015 of a provision related to the restructuring of our finance and accounting function and the closure of our office in Quebec City, as well as the realization of cost savings in connection with the restructuring. The comparative decrease for the twelve-month period is also explained by certain transaction costs allocated to warrants in connection with the completion of share issuances in March and December 2015.
Selling Expenses
Selling expenses were $1.5 million and $6.7 million for the three and twelve months ended December 31, 2016, respectively, as compared to $1.8 million and $6.9 million for the same periods in 2015. Selling expenses for the three and twelve months ended December 31, 2016 and 2015 represent mainly the costs of our contracted sales force related to our co-promotion activities as well as our internal sales management team. Selling expenses remained relatively stable during 2016.
Net Finance (Costs) Income
Net finance (costs) income were $(622,000) and $4.5 million for the three and twelve months ended December 31, 2016, as compared to $(185,000) and $(15.3) million, for the same periods in 2015. The increases in finance income or decreases in finance costs were mainly attributable to the change in fair value recorded in connection with our warrant liability. Such change in fair value results from the periodic "mark-to-market" revaluation, via the application of option pricing models, of outstanding share purchase warrants. During 2016, the "mark-to-market" warrant valuation was impacted by the expiration of the remaining Series B Warrants. During 2015, the change in assumptions that were applied to determine the fair value of the alternate cashless feature included in the Series B Warrants significantly impacted the "mark-to-market" valuation. Furthermore, the closing price of our common shares, which, on the NASDAQ, fluctuated from $3.25 to $4.94 during the three-month period and $2.67 to $4.94 during the twelve-month period ended December 31, 2016, respectively, compared to $4.00 to $11.43 and $4.00 to $84.20 during the same periods in 2015, also had a direct impact on the change in fair value of warrant liability. In addition, with specific reference to 2015, finance costs were also impacted by the warrant exercise inducement fee paid to certain holders of the Series B Warrants.
Net Loss
Net loss for the three and twelve months ended December 31, 2016 was $(8.2) million and $(25.0) million, or $(0.71) and $(2.41) per basic and diluted share, as compared to a net loss of $(10.0) million and $(50.1) million, or $(1.46) and $(18.14) per basic and diluted share, for the same periods in 2015. The decrease in net loss for the three months ended December 31, 2016, as compared to the same period in 2015, is due largely to lower G&A expenses, as presented above. The decrease in net loss for the twelve months ended December 31, 2016, as compared to the same period in 2015, is due largely to lower operating expenses and higher comparative net finance income, as presented above.
Liquidity
Cash and cash equivalents were $22.0 million as at December 31, 2016, as compared to $41.5 million as at December 31, 2015. The decrease in cash and cash equivalents as at December 31, 2016, as compared to December 31, 2015, is mainly due to the net cash used in operating activities. The decrease was partially offset by the net proceeds generated by the sale and issuance of common shares and warrants during 2016.
Conference Call & Webcast
The Company will host a conference call and live webcast to discuss these results on Thursday, March 16, 2017, at 8:30 a.m., Eastern Time. Participants may access the live webcast via the Company's website at www.aezsinc.com or by telephone using the following dial-in number: 201-689-8029 and Confirmation number 13653427. A replay of the webcast will also be available on the Company's website for a period of 30 days.
For reference, the Management's Discussion and Analysis of Financial Condition and Results of Operations for the fourth quarter and full year 2016, as well as the Company's audited consolidated financial statements as at December 31, 2016, 2015 and 2014, can be found at www.aezsinc.com in the "Investors" section.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a specialty biopharmaceutical company engaged in developing and commercializing novel treatments in oncology, endocrinology and women's health. We are engaged in drug development activities and in the promotion of products for others. We recently completed Phase 3 studies of two internally developed compounds. The focus of our business development efforts is the acquisition of licenses to products that are relevant to our therapeutic areas of focus. We also intend to license out certain commercial rights of internally developed products to licensees in non-U.S. territories where such out-licensing would enable us to ensure development, registration and launch of our product candidates. Our goal is to become a growth-oriented specialty biopharmaceutical company by pursuing successful development and commercialization of our product portfolio, achieving successful commercial presence and growth, while consistently delivering value to our shareholders, employees and the medical providers and patients who will benefit from our products. For more information, visit www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made pursuant to the safe-harbor provision of the U.S. Securities Litigation Reform Act of 1995, which reflect our current expectations regarding future events. Forward-looking statements may include, but are not limited to statements preceded by, followed by, or that include the words "expects," "believes," "intends," "anticipates," and similar terms that relate to future events, performance, or our results. Forward-looking statements involve known risks and uncertainties, many of which are discussed under the caption "Key Information - Risk Factors" in our most recent Annual Report on Form 20-F filed with the relevant Canadian securities regulatory authorities in lieu of an annual information form and with the U.S. Securities and Exchange Commission ("SEC"). Such statements include, but are not limited to, statements about the progress of our research, development and clinical trials and the timing of, and prospects for, regulatory approval and commercialization of our product candidates, the timing of expected results of our studies, anticipated results of these studies, statements about the status of our efforts to establish a commercial operation and to obtain the right to promote or sell products that we did not develop and estimates regarding our capital requirements and our needs for, and our ability to obtain, additional financing. Known and unknown risks and uncertainties could cause our actual results to differ materially from those in forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue our research and development projects and clinical trials, the successful and timely completion of clinical studies, the risk that safety and efficacy data from any of our Phase 3 trials may not coincide with the data analyses from previously reported Phase 1 and/or Phase 2 clinical trials, the rejection or non-acceptance of any new drug application by one or more regulatory authorities and, more generally, uncertainties related to the regulatory process (including whether or not the regulatory authorities will accept the Company's conclusions regarding Macrilen™ following its comprehensive review of the Phase 3 study data described elsewhere in this press release), the ability of the Company to efficiently commercialize one or more of its products or product candidates, the degree of market acceptance once our products are approved for commercialization, our ability to take advantage of business opportunities in the pharmaceutical industry, our ability to protect our intellectual property, the potential of liability arising from shareholder lawsuits and general changes in economic conditions. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties. Given these uncertainties and risk factors, readers are cautioned not to place undue reliance on these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law.
Consolidated Statements of Comprehensive Loss Information
(omitted)
_________________________
1. Approximately $1.5 million was denominated in EUR as at December 31, 2016 and December 31, 2015, and approximately $3.7 and $4.4 million were denominated in Canadian dollars as at December 31, 2016 and December 31, 2015, respectively.
2. Approximately $0.6 million was related to our provision for restructuring as at December 31, 2015.
3. Comprised mainly of employee future benefits, provisions for onerous contracts and non-current portion of deferred revenues.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170315006476/en/
Source: Aeterna Zentaris Inc.
Read more: http://www.nasdaq.com/press-release/aeterna-zentaris-reports-fourth-quarter-and-fullyear-2016-financial-and-operating-results-20170315-01242#ixzz4bQiLtwqr
______________________________________________
AEZS
Out GIII @ $24.87. Think can get back in lower in the future. Trading very choppy considering its low Beta. Shorts are at the highest level in one year.
GIII
Bristol-Myers Squibb (BMY) Presents at Barclays Global Healthcare Broker Conference (Transcript)
Mar. 15, 2017 1:17 PM ET| About: Bristol-Myers Squibb Company (BMY)
Bristol-Myers Squibb Co (NYSE:BMY)
Barclays Global Healthcare Broker Conference Call
March 15, 2017, 08:30 ET
Executives
Charlie Bancroft - EVP & CFO
Analysts
Geoff Meachem - Barclays Capital
Geoff Meachem
Good morning, welcome to the second day of the Barclays Global Healthcare Conference. My name is Geoff Meachem, I'm a senior biopharma analyst and I have Paul Choi from my team as well with me on stage here. And it's our pleasure to have Bristol-Myers on stage. And speaking on behalf of Bristol is Charlie Bancroft, CFO. Charlie, welcome.
Charlie Bancroft
Thanks for having me, Geoff.
Geoff Meachem
So if you want to start off with a couple of high-level comments and then we can get ready some questions.
Charlie Bancroft
Sure. Bristol-Myers Squibb is in interesting time where we find ourselves in a very competitive second-line lung market. The first-line lung market continues to evolve in competitive dynamics there. We'll continue to evolve as we think about Merck getting approved in the high expressers last year-to-centric now in second-line in all-comers. Merck is actually getting improved in Keytruda chemo combo for first-line.
So we see that dynamic, but we still feel based on our broad portfolio, not only in lung but across IO that we have significant opportunities and we'll be a meaningful player even in the lung market. But we realize that, we have a broad program and some of that still has to read out over time and its competitive dynamics still are evolving.
We also have a portfolio that continues to grow outside of oncology. So if you look at Eliquis is a big driver for us orencia continues to grow well, Sprycel even though slightly older product, continues to grow well. And then if you look at our pipeline, both in oncology and non-oncology - and I'm sure you have some questions on that, we see some really interesting opportunities in areas what we determine as high unmet medical need and the potential for high treatment effect, because that's really important when you think about the value proposition and trying to make an unambiguous for payers that there's a real opportunity there.
So we're really excited about what we have coming forward, but we do appreciate that with the competitive environment we find ourselves.
Geoff Meachem
Perfect. Let's start first with the commercial IO business. I know part of the thesis for this year is that you'll see IO growth in the U.S. And I wanted to get a perspective from you Charlie on the second-line lung market. What are you seeing now, what would you expect to see with perspective to market share at the sort of exit of this year and how important is getting the - say, market expansion and incremental share, let's say in Europe to the whole IO growth for 2017?
Charlie Bancroft
Sure. The second line lung market is still very important for us. And as we think about exiting out of 2016 into this year, we find that our shares right now are fairly stable. The biggest impact in the fourth quarter really came from the centric, but by and large our shares are stable. And interestingly even in first line, our non-promoted sales were still seeing mid-single-digits in non-promoted sales. As I mentioned, just a few minutes ago, it will continue to become more and more competitive and as Merck potentially gets approved with their Keytruda chemo combo, in May, that will in some way shrink the second line market as there's more patients in the front line setting.
And we continue to see testing for high-expressers, we're testing for TDL 1 I should say and Merck approved in high-expressers in the front line also will continue to shrink. So the second line setting is still going to be extremely competitive. Now, internationally, we don't have that - Merck will likely get approved 024 in some markets in the early approval markets in 2017. But we see that we started significant ramp still now outside the U.S.
So as we've mentioned previously, we expect to grow IO internationally and we expect that in the U.S. will potentially remain flat overall for IO because if we think about the rest of the opportunities that we have, because we resourced for a month earlier this year with the anticipation that we would get approved on 026. So we really focused those resources on defending the second line of gaining share in melanoma also expanding an increasing share in renal cell and then of course we're launching head and neck and bladder.
For example, just on melanoma, for example, we have in the regimen 30% to 40% of first line market, but in BRAF positive patient it's actually far below that. And given our data that should be a big opportunity, so we think we can still drive opportunity in melanoma. In renal cell, we had a really good start, our share dipped down a little bit, but now it's rebounded to 60%. Just several months ago, it was 40%. So we're seeing good continued growth in renal cell and we see combo now primarily being used at this stage in third line. So we still see lots of opportunity across our portfolio. When we launched - head and neck was launched and as we see uptick in that and bladder, we can hope to see strong growth across the rest of our portfolio outside of lung.
Geoff Meachem
So, if second line lung contracts this year, in the U.S., do you see enough growth from Hodgkin lymphoma, renal, head and neck, et cetera, melanoma, to offset that? Or is it really about lung being by far the bigger contributor to the business?
Charlie Bancroft
Like I said, I think we'll see pressure upon the second-line, for us, I think it will be offset by and large, by growth in the other tumor types. So net-net, we see that our IO business in the U.S., let's say roughly flat year-over-year.
Question-and-Answer Session
Q - Unidentified Analyst
Perhaps pivoting to the clinical trial side and thinking about the lung trials here, obviously a big focal point with investors is 227. And so maybe you can sort of walk us through what some of the milestones might be in terms of potential look this year, how and when those might read-out. And as you potentially do better in interim looks, what are sort of implications perhaps from a statistical perspective, whether you guys may or may not take a hit and how that factors into your potential registrational strategy.
Charlie Bancroft
Sure. Thanks. So we have by far the broadest program in first-line lung when you look at 227 and 568. And at the heart of our strategy is still Opdivo-Yervoy combination and we think there's strong potential in that. But we also are testing Opdivo and chemo, we're testing Opdivo-Yervoy plus chemo and that could potentially address early progresses.
So we feel that we still have meaningful opportunity as we think about our lung program. As it relates to when the trial will read-out, it's posted on clinicaltrials.gov, it's early 2018. We have said that we do have a planned interim look, but at this stage, I don't think it's [indiscernible] time for that. And we didn't - as we said, spend any statistical alpha in 227.
Geoff Meachem
Just with respect to IO combinations beyond ipi/nivo, would you say that Bristol is still - are you at capacity, would you be looking to add more assets that are combinations in IO? And obviously you guys are pretty far along when it comes to novel mechanisms, LAG-3 care, et cetera. But how much is enough from a capacity standpoint?
Charlie Bancroft
It's a good question, because I'm also responsible for business development. Every time we think that we have enough, there is always something else. So the science here continues to evolve and it continues to evolve rapidly. We have, besides Opdivo and Yervoy, two approved products, we have - I might get this wrong, but 10 or 11 other molecules in development.
So I'm not sure given where the marketplace is going and the market is going to eventually go to a very segmented patient population. And when you look at the future, it's going to be differentiated on patient selection and segmentation. So when you think about that translational medicine, understanding the underlying biology, when you think about biomarkers and having the capabilities and skills there gives you better insights into what kind of development plans will help quickly progress the programs in a more rational way than an empirical way, but then also very importantly on the commercial side, from a value standpoint, how do we think about these from really targeted value based medicine standpoint to identify the right patients for the right medicine.
So that's where the industry is going, that's where we're going, we're spending a lot of time in energy in continuing to build our capabilities in translational medicine and biomarkers mostly through third-party partnerships, but we view that that's going to be where ultimately as you think about where this industry is going to go. It's going to be much more segmentation, because if you look at the standard of care today even in lung cancer, there are still based on all the clinical trials, a lot of room to raise the standard of care. So from a business development side and looking at assets, I think we'll always do that. I think oncology is so important to us and the ability to continue to drive and defend our position, but also grow, it's imperative that we continue to drive in business develop.
Geoff Meachem
And along those lines, what's your perspective, Charlie, on the pricing debate? A lot of folks on oncology say that adding incremental regimens to a combination ultimately is not going to be cost-efficient. And the answer from some of your peers across the pharma space, they talked about owning all the assets in a bundle, is that still - philosophically, do you agree with that?
Charlie Bancroft
I'll come to that. I think the answer to that is yes, because it provides you much more optionality, but I would go back to what I was just saying at the heart of the pricing discussion is value. So where you can show value and where you can show value in a real way, you'll be able to get price. And again, I think it's going to come back to segmentation, patient selection really showing long-term durable results. And you'll be able to think of pricing in different way. It's more about how do you think about value. Now having said that, we firmly believe that having more of the assets and the combined ability of assets internally as a strategic imperative and as a strategic - provides us more strategic optionality as we think about pricing, I don't want to talk about pricing of unapproved products at this stage, but we do feel that it will provide more optionality for us.
Geoff Meachem
Maybe switching gears, outside of lung, you, Bristol will have actually pretty data-rich 2017, 2018. So as we look at the next 12, 18, 24 months, you're going to have multiple tumor types reading out beyond lung and melanoma that could potentially add the label. As we think about the mix of Opdivo revenue changing over time, what kind of contribution can these tumor types that are coming up in terms of data readout potentially be as a mix of potential peak sales versus most people assume lung is the bulk of sales followed by melanoma and so forth. So how should we think about potentially modeling over time, what these tumor types could add in terms of revenue to your Opdivo franchise?
Charlie Bancroft
Sure. I'm not going to give you any forward-looking, but I can kind of frame it. I think, taking a step back, if you think about the biggest opportunity from unmet medical need in epidemiology, still lung is important. Given our program, we still feel open opportunities in the lung market. But beyond that, if you look at the other tumor types where we've competed in melanoma, we've done quite well. We've launched well in renal cell, we've now launched in head and neck and bladder. The opportunities we see as we think about two, three registrational trials that we have breaking out in the next 12 months or so. So we have epicellular cancer in line with Opdivo. We have the regimen for both renal cell and first line in non-small cell lung cancer in the front line setting.
And then if you look at our entire development program, it's quite a large if you look at the number of readouts that we'll have over the next several years. So each tumor type really, I always say, it depends on the data, because the data in the competitive environment will really drive how much we think each of those will generate as far as sales. And our view is that any individual one could be fairly big but collectively outside of lung they will be meaningful. And that's how we look at it.
Geoff Meachem
And Charlie, when you think about the - we talked earlier about the international components. So far, I know it's much earlier than the U.S. kind of roll out, but so far is there any things that you'd point to that differs sort of European versus U.S. with regard to testing or adoption, that give you kind of maybe a different perspective in terms of what the peak trajectory or the trajectory of peak opportunity.
Charlie Bancroft
One of the things that surprised us initially when we launched in the U.S. was the time to peak sales as we were modeling it in most of the indications in which we've competed. And so as we now look in Europe which is a little bit different dynamic in that pricing access and reimbursement paradigms is slightly different, you have some early access markets where you have access then you have other ones where it's much more controlled than if you want to take, the UK is one of the more challenging ones.
Some of the HPA markets it can be a challenge, but where we have and gotten approval and we've gotten a lot of approvals over the course of the last couple years, we continue to see not surprised anymore, but we continue to see peak - time to peak sale is actually continues to be very, very strong. So, the competitive environment is still robust in all these markets, some of the markets have more of - I would call a hierarchy of how you - when you can introduce IO, it's a little bit more stringent than sometimes in the U.S. But we think our international business as we mentioned is going to grow quite significantly in IO this year, year-over-year.
Geoff Meachem
Maybe switching gears outside of IO for now, as we think about the non-IO pipeline which had become a more prominent part of the discussion with regard to Bristol, at what point - how do we think about the areas you're working in terms of like heart failure, the autoimmune assets and things like fibrosis becoming more available in terms of data when we should start to see potential read-outs for those and how do you think about those over the long-term being contributors and diversifying new revenue mix?
Charlie Bancroft
Sure. We're very excited about our early pipeline in oncology and outside of oncology. And we believe that if you look at IO growth - I'm going to get you answer for your question. If you look at our growth over the next three to four years, it's really driven by IO and Eliquis by and large. So for us strategically diversifying is something that's really important for us.
And as we allocate our R&D dollars, we're very focused on driving towards those assets that we feel address a high unmet medical need, that have high treatment effect and in many ways will be unambiguous to payers that there is opportunity for value there. So, getting to your question, we're going to present data at upcoming at EASL on FGF21 for the liver fibrosis, for example, that's a very exciting opportunity for us and what could be a very large market as you know.
In heart failure, we have the nitroxyl donor that's in Phase II. I'm not sure when we'll see the pivotal data on that, but that's for decompensated heart failure and that's also a very big market for us. In immunoscience, we have [indiscernible] for psoriasis that could also be a potential big opportunity in Lupus. That we'll see data potentially at the end of this year.
And we have the BTK inhibitor for RA which we expect to see data early next year. All of those things dependent up on data of course could pivot into a registrational study.
Geoff Meachem
Also outside of IO, when you look at Eliquis business, obviously the growth has been fantastic, the share gains have been quite good. But I think that the tipping point though to me still seems like the warfarin getting share from that. So is there either data or physician comfort or is there some sort of inflection point that you would see over time that could move you to capture that bigger part of market?
Charlie Bancroft
We're extremely happy with Eliquis and we don't get a lot of questions anymore in the market, but if you look at the growth that we've had and you look at potential for growth going forward, it's still quite great. In large part, it's because if you look at the safety and efficacy data that we have based on our clinical trials and the growing amount of real world evidence, it's quite striking and that's where we're seeing the growth for Eliquis.
And even as an example as we work with some of the plans in the U.S. the medical teams that has managed care components, they really focus on the real world data and that's been a big benefit for us as we think about those particular plans. We still feel there's opportunity in growing against the other NOACs but also against warfarin which today in the U.S. represents about 40% of the overall market. And I'll give you some examples, in the U.S. right now, Eliquis is the Number 1 TRx in the NOAC clients. But if I look at cardiology and working with cardiologists which is sort of the precursor to the broader population, we lead in TRx across the entire class including warfarin.
So we feel that there's still a big opportunity based on good clinical data, continued growing real world evidence, they continue to make inroads both in warfarin, but also against the other NOACs. And we're doing that without really in anyway growing the expenses related to Eliquis. So it's really very, very focused targeted including DTC as we've seen in the U.S. that's in extremely - has a really good ROI for us and that's helping also with warfarin usage.
Geoff Meachem
To Paul's question earlier about assets outside of IO and Eliquis well, is there a philosophy, Charlie, about stated goal of trying to diversify the business in a broad way from state of [indiscernible] perspective. My guess here is that a lot of companies are waiting for more clarity on tax reform, repatriation, things like that. That may be a tipping point for some, but I get the sense that if there is a need to do a deal, than that would kind of override any kind of near-term fluctuation on the Washington side of things.
Charlie Bancroft
We look at diversification in two ways and I think you're touching on that. One is to continue to grow our entire pipeline. So if diversification within other tumor types, even within immuno-oncology, we talked about the number of assets that we have there in which to do that, continue to build out our translational medicine and be leaders and how we think about translational medicine and new biomarkers, so we can continue to segment patients. It's also about diversifying through building out our non-oncology portfolio and I talked with Paul a little bit about the assets that we have there.
From a business development standpoint, we're always looking at opportunities. And quite frankly, we look at opportunities from the largest to the smallest and we do that on a regular basis. And we do it though I would say, majority is within our core therapeutic areas where we have deep understanding of the science where we can be synergistic with some of our - potentially with our current assets, it can be synergistic with knowledge base that we have. It can be synergistic with the commercial infrastructure that we have.
It's always hard to talk about BD, but I would say that we've always been very active. Where we found the best value though, by and large, has been early. So when you look at the risk-reward trade-off of the assets, I don't want to say things are fulsomely priced in the later stage, but if becomes a little bit more challenging from a valuation perspective. But we find it early, because it really doesn't cost that much. If it works, it's great, if it doesn't, that's just part of our business model.
Geoff Meachem
Another part of the business, obviously the focus tends to remain on IO and Opdivo, but another very well performing business has been Orencia for you. And unlike some of the - anti-chain assets have been sort of focused on targets for biosimilars. It seems like Orencia is largely flying under the radar with respect to competitive threats there.
Can you talk a little bit maybe about how you see growth continuing for that franchise, a time here there are some lumpiness between sub Q and IV formulations. And maybe does that market and product line continue to look like at the current growth rate for you going forward?
Charlie Bancroft
A lot of questions are packed in there. Orencia - again not exactly get a lot of questions on this generally, but it has been a strong growth brand, growth franchise for us when you think about the sub Q and IV. We've been really focused because of the data that we have on the rapid early progressers in RA. And that message has been resonating well with the prescribing physicians because you continue to see that Orencia is moving up the treatment paradigm of the recycling of TNFs.
So recycling at times orencia keeps moving up that treatment paradigm. So we're very pleased with that and we have a lot of good evidence there. We continue to invest. I think the composition of matter patent for Orencia is 2019 and the method of use is 2021, thereabouts. Our resourcing model has biosimilars in the market either directly against Orencia. So orencia is not a TNF, so it actually has its own area to play in. But if we do get biosimilars which we expect we will and that's within our planning horizon, we will resource Orencia accordingly based upon the market dynamics.
Geoff Meachem
Charlie, thank you very much.
Charlie Bancroft
Thank you.
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http://seekingalpha.com/article/4055442-bristol-myers-squibb-bmy-presents-barclays-global-healthcare-broker-conference-transcript?part=single
BMY
You are right. Maybe folks are waiting until after this evening when the quarterlies are out. Also, I believe a lot of folks won't touch AEZS because of the bad reputation.
50 Day Avg. Daily Volume 285,381
Read more: http://www.nasdaq.com/symbol/aezs#ixzz4bOnp2RII
Actual
Date Open High Low Close / Last Volume
03/14/2017 3.05 3.05 2.85 2.9 208,613
03/13/2017 3.05 3.15 2.95 3 138,500
03/10/2017 3.1 3.15 3 3.05 176,799
03/09/2017 3.2 3.2 3.1 3.1 108,101
03/08/2017 3.2 3.2 3.05 3.1 73,893
03/07/2017 3.2 3.3 3 3.1 208,473
03/06/2017 3 3.1 2.9 3.05 113,849
03/03/2017 3.1 3.3 3 3 137,038
03/02/2017 3 3.1 3 3.1 148,156
03/01/2017 3.05 3.1 3 3 129,140
02/28/2017 3 3.11 3 3.05 95,851
02/27/2017 3 3.1 3 3.05 89,582
02/24/2017 3.1 3.1 3 3 120,630
02/23/2017 3.05 3.175 3.05 3.15 92,921
02/22/2017 3.2 3.25 3.05 3.1 211,156
Read more: http://www.nasdaq.com/symbol/aezs/historical#ixzz4bOmkFOcp
(I have no shares)
AEZS
Two documents updated in the iBox. AEZS has recently updated their FACT SHEET to March, 2017. Also, changed Corporate Presentation to Company Overview, dated February 2017.
AEZS
Out SONS @ $6.24. Chart remains great and intend to get back in, but the easy rise could be over.
SONS
Jefferies Expects a Bristol-Myers Squibb Bounce
Another drug stock Jefferies weighed in on was BMY, with the brokerage firm setting a price target of $66. This represents 15.6% upside to BMY's Wednesday close at $57.12, and territory not seen since before an August bear gap. Nevertheless, Bristol-Myers Squibb Co shares are trading slightly lower ahead of the bell, on track to add to their roughly 14% year-to-date deficit. Should upbeat analysts begin to change their tune, the stock could see additional technical trouble. Currently, eight of 13 brokerages maintain a "buy" or better rating, leaving the door wide open for downgrades.
http://www.schaeffersresearch.com/content/news/2017/03/09/johnson-johnson-merck-bristol-myers-squibb-upgraded?utm_source=SM&utm_medium=Link&utm_campaign=Twitter
BMY
You have played it right so far and I believe what you are saying, but I'm still waiting to see how it trades with the big open gap from the gap-up.
I'm sure you saw the Fly story yesterday:
Nimble Storage could still be 'in play,' says Maxim Maxim analyst Nehal Chokshi recommends investors hold on to shares of Nimble Storage (NMBL) after the company announced a deal to be acquired by Hewlett Packard Enterprise (HPE) as he believes the company may still be "in play." He views Microsoft (MSFT), Cisco (CSCO) and NetApp (NTAP) as among other potential suitors for Nimble and adds that the $40M break up fee "is not too significant" to prevent other suitors from stepping in. The analyst, who has a $14 price target on Nimble based on its stand-alone value, added that the takeover price it garnered reflects positively on the valuation of peer Pure Storage (PSTG). Nimble shares closed yesterday at $12.58, above HP's $12.50 per share bid.
Read more at:
http://thefly.com/landingPageNews.php?id=2517136
PSTG
Entire release:
Bristol-Myers Squibb Appoints Dr. Thomas J. Lynch, Jr., Executive Vice President and Chief Scientific Officer
03/08/2017
NEW YORK--(BUSINESS WIRE)--
Bristol-Myers Squibb Company (NYSE:BMY) today announced that it has appointed Dr. Thomas J. Lynch, Jr., 56, executive vice president and chief scientific officer, effective March 16, 2017. He succeeds Dr. Francis Cuss, 62, who will retire from the company. Dr. Cuss will serve as an advisor to the company for the next three months to ensure a seamless transition. In connection with today’s announcement, Dr. Lynch will step down from the Board of Directors of Bristol-Myers Squibb, effective March 15, 2017.
Dr. Lynch has more than 30 years of medical, management and leadership experience, including more than 23 years at Massachusetts General Hospital (MGH). He served as chairman and chief executive officer of Massachusetts General Physicians Organization and as a member of the MGH Board from 2015 to 2017. Before returning to MGH, Dr. Lynch served as the director of Yale Cancer Center and was the Richard and Jonathan Sackler Professor of Internal Medicine at the Yale School of Medicine from 2009 to 2015. While at MGH in 2004, Dr. Lynch was part of the team credited with the significant discovery that certain genetic mutations in lung cancer patients caused therapies to work for some individuals and not for others.
“We are pleased to welcome Tom to the leadership team at Bristol-Myers Squibb,” said Giovanni Caforio, M.D., chief executive officer and chairman designate of Bristol-Myers Squibb. “Tom is an internationally recognized oncologist known for his leadership in the treatment of lung cancer and has made significant contributions to the field of targeted therapies throughout his career. Tom brings deep industry knowledge and a sophisticated understanding of the Bristol-Myers Squibb Research & Development program from his experience as a member of our Board. As we transition to our next phase of growth, we are confident Tom is the right person to lead our dynamic R&D organization as we focus on accelerating the development of our Immuno-Oncology medicines and fully realizing the extraordinary potential of our diverse, innovative pipeline. With deep experience as a clinical researcher, leader of large research centers and a practicing physician, Tom brings unique, important and timely perspectives to the business.”
Dr. Lynch said, “Throughout my career, I have been devoted to advancing oncology research, with a particular focus on lung cancer. I have seen firsthand Bristol-Myers Squibb’s commitment to making a meaningful difference in the lives of patients, and I am honored to lead the company’s R&D program, where lung cancer research is a core area of focus in a highly successful Immuno-Oncology development program. I have a strong appreciation for the depth of Bristol-Myers Squibb’s portfolio and rich pipeline in oncology as well as in the fields of cardiovascular diseases, immunoscience and fibrosis. We have a number of significant opportunities and are uniquely positioned to transform cancer care. I am confident that our team will continue to discover and develop innovative medicines that address serious diseases in areas of significant unmet medical need.”
Caforio concluded, “On behalf of the Board and leadership team, I want to thank Francis for his hard work and dedication to Bristol-Myers Squibb for more than 13 years. Our portfolio and pipeline have been significantly strengthened during his time leading Discovery and R&D, and we wish him the best in his retirement.”
“It has been an honor to lead Bristol-Myers Squibb’s talented R&D team during such a transformative period for the company,” said Cuss. “Today, Bristol-Myers Squibb is creating unprecedented opportunities to address some of the most challenging disease areas in ways we never thought possible even five years ago. I’ve come to know Tom well in his capacity as a board member and I am confident that under his leadership the team will continue to flourish and find new ways to discover, develop and deliver innovative medicines that make a difference in the lives of patients.”
About Dr. Thomas J. Lynch, Jr.
Dr. Lynch has served as chairman and chief executive officer of Massachusetts General Physicians Organization and a member of the Massachusetts General Hospital Board since 2015. From 2009 to 2015, Dr. Lynch was director of Yale Cancer Center and was the Richard and Jonathan Sackler Professor of Internal Medicine, Yale Cancer Center, Yale School of Medicine. He has also served as the Physician in Chief of Smilow Cancer Hospital, Yale-New Haven, since 2009. Prior to 2009, Dr. Lynch was Professor of Medicine at Harvard Medical School and chief of Hematology/Oncology at Massachusetts General Hospital. Dr. Lynch is a member of the American Association for Cancer Research, the American Society of Clinical Oncology, and the International Association for the Study of Lung Cancer.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
Statement on Cautionary Factors
This Report contains certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans and projections regarding the company’s financial position, results of operations, market position, product development and business strategy. These statements may be identified by the fact that they use words such as "anticipate", "estimates", "should", "expect", "guidance", "project", "intend", "plan", "believe" and other words and terms of similar meaning in connection with any discussion of future operating or financial performance. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations.
These factors include, among other things, effects of the continuing implementation of governmental laws and regulations related to Medicare, Medicaid, Medicaid managed care organizations and entities under the Public Health Service 340B program, pharmaceutical rebates and reimbursement, market factors, competitive product development and approvals, pricing controls and pressures (including changes in rules and practices of managed care groups and institutional and governmental purchasers), economic conditions such as interest rate and currency exchange rate fluctuations, judicial decisions, claims and concerns that may arise regarding the safety and efficacy of in-line products and product candidates, changes to wholesaler inventory levels, variability in data provided by third parties, changes in, and interpretation of, governmental regulations and legislation affecting domestic or foreign operations, including tax obligations, changes to business or tax planning strategies, difficulties and delays in product development, manufacturing or sales including any potential future recalls, patent positions, the ultimate outcome of any litigation matter, our level of indebtedness and risks, disruption, costs and uncertainty caused by or related to the actions of stockholders. These factors also include the Company’s ability to execute successfully its strategic plans, including its business development strategy, the expiration of patents or data protection on certain products, including assumptions about the Company’s ability to retain patent exclusivity of certain products, and the impact and result of governmental investigations. There can be no guarantees with respect to pipeline products that future clinical studies will support the data described in this release, that the compounds will receive necessary regulatory approvals, or that they will prove to be commercially successful; nor are there guarantees that regulatory approvals will be sought, or sought within currently expected timeframes, or that contractual milestones will be achieved. For further details and a discussion of these and other risks and uncertainties, see the Company's periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the SEC. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170308006069/en/
Source: Bristol-Myers Squibb Company
Good for you -- you expecting it? I was getting ready for the day and missed the early run-up here, but sold a few minutes ago at $10.15 for a little profit. I've seen buyout speculation about PSTG also.
PSTG
Bristol-Myers Squibb (BMY) CEO Giovanni Caforio Presents at Cowen and Company 37th Annual Health Care Conference (Transcript)
Mar. 6, 2017 4:06 PM ET| About: Bristol-Myers Squibb Company (BMY)
Bristol-Myers Squibb Company (NYSE:BMY)
Cowen and Company 37th Annual Health Care Conference Call
March 06, 2017 02:00 PM ET
Executives
Giovanni Caforio - CEO
Analysts
Steve Scala - Cowen & Co.
Steve Scala
Good afternoon, I’d like to welcome Bristol-Myers Squibb to the Cowen Conference representing the company is Giovanni Caforio, who is the Chief Executive Officer, also here from the company is John Elicker, In-charge of Investor Relations.
Before I turn it over to Giovanni, I would like to remind you of the analysis that we put out last Monday, which was our statistical modeling exercise of CheckMate-227. Which concluded that should Bristol work in Q3 on an interim bases at the expresser group in 227. It will stop by our calculations with near certainty. So, that would reestablish Bristol as an extremely important company in all lines of lung cancer. So, four, five months from now that would be our forecast.
So with that I will turn it over to Giovanni.
Giovanni Caforio
Thank you, Steve and good afternoon, everyone. It’s great to be here, let me take this opportunity to give you an update on where we are as a company. What is happening, how our strategy is evolving and most importantly the progress we’re making with executing our strategy.
If I can have the first slide, this one. Okay, that's our forward-looking information… perfect. So, I always start with this slide, this is a slide that I believe once won’t be new to many of you it clearly describes our strategy as a company. A strategy that we adopted in 2007 and I would say that our company has evolved substantially over the last few years and continues to evolve. But we remain very committed to many of the word you see on this slide.
Today we are differentiated by a pharma company with transformational assets in areas of high unmet medical need we’ll cover many of those. A company with deep R&D expertise and business development capabilities; and I believe that thanks to the investments we’ve made in order to acquire a good scale and comparative presence in oncology and other markets in which we compete we are uniquely scaled and resourced for growth going forward.
I would like to cover a few topics that relates to R&D productivity, the commercial execution of Bristol-Myers Squibb, discuss with you the work ongoing and streamlining our operating model and also describe our financial strength and flexibility.
So, starting with R&D productivity, our organization is focused on leading science, the majority of our programs are first in class, many can be best in class agents. And we’ve had great success over the last few years in renewing our portfolio of market at medicines. Today we have what we call a very fresh portfolio of medicines in the market with remaining substantial opportunity for growth going forward.
With respect to productivity, the numbers are clear in terms of new approvals coming into the market over the last few years. Our R&D organization has been consistently above benchmark. And finally with significant investment in R&D of over $4 billion per year, our level spend is comparable to be peer group companies. And clearly we are committed to continuing to invest in the right type of R&D activity.
Looking at immuno-oncology specifically, obviously that is an area of very significant focus for the company. I’m sure it is clearly the area that attracts the most attention and questions from investors and shareholders. Let me just say in the last three years since the first approval of Opdivo, our success with broadening the number of indications for Opdivo and bringing forward truly innovative science has been remarkable.
You see some metrics here, Opdivo today is approved in a bit over two year in 11 indications in the United States alone and we’ve had over 100 approvals globally. Scientifically, 15 of our registrational trials have been positive and obviously one as you know has been negative last year. Five of our Phase III trial were stopped early because of survival advantage and we have ongoing programs in 14 tumor types that have the potential for data read outs in the short and the medium term.
From the perspective of advancing science, we’d like to reference the number of New England Journal Medicine’s publication and the number of breakthrough therapy designations for Opdivo, commercially also and particular, when you think about the results of last year.
The company is executing very effectively last year as a total company, we were able to grow our top-line 17%, our earnings per share in '16 grew 40% versus 2015. And that was thanks to very strong performance across the board both in terms of therapeutic areas, in terms of products and geographies.
You see some numbers here Opdivo grew and together with Yervoy our immune-oncology franchise reached $4.8 billion in sales. I'm actually very pleased with the performance of Eliquis, which grew 80% in the market last year and became the leading agent within its approved indications in the cardiology space in the U.S. where we are actually the leading agent in TRXs in the total oral anticoagulant market including warfarin and we continue to progress our leadership in terms of NBRXs, TRXs not only in the total market in the US but also in multiple countries around the world.
And finally, strong performance with our Orencia and Sprycel some of the more established brands both growing double-digit, again this reflects the strength of our execution commercially on a global basis. I'll make a couple of comments about our operating model transformation, obviously the company has grown last year substantially as I just showed you. And there is a very good momentum from a pipeline perspective and from a commercial perspective.
About a year ago we made a decision to really challenge the way we operate as a company and allocation resources and the objective was twofold, it was really first to ensure that we had a model in place where we could allocate all of our resources to the highest priorities. And second, that we could continue as a company to move fast and operate successfully in a very competitive and dynamic marketplace.
And so we put in place a number of changes that will be executed over the last two to three years and the changes are aimed at allocating more resources to top brands in key markets, I'll remind you that 9 brands in 20 markets account for more than 90% of Bristol-Myers Squibb today. We integrated our oncology model, from a model in which we had two separate organizations for early oncology and full developments to one that works across the full spectrum of development activities.
We decided to create a much more entrepreneurial dynamic fast moving unit to accelerate some of our assets outside of oncology. We believe there is more opportunity for us to focus resources in manufacturing of biologics. And so at the same time in which we are building a large scale facility in Ireland we’ve decided to look at ways of variabilizing [ph] and streamlining our small molecule network. And obviously we are doing a lot of work to make our G&A functions cost effective and tailored to the company we are today.
The net result of this, as I said at the beginning must be a more effective and comparative company, but we are also able to maintain our total OpEx flat. And in fact four example this year we guided to flat OpEx versus last year, but within that we were able to significantly increase our investment in R&D.
Finally we are focused on shareholder value creation. We actually have a long history of successfully creating value for shareholder. We maintain a very strong balance sheet with cash and equivalents of approximately $9 million, of which 85% is internationally. We decided to opportunistically initiate a $2 billion share repurchase program and have a 10b5-1 approved and in place.
We remain committed to the dividend, which has been increased at the end of last year for the 8th consecutive year. And most importantly the balance of our capital allocation strategy enables us to continue to think about business development as one of the key strategic levers for the company.
Our 2017 priorities look very similar to the priorities I presented last year. The first one really is about driving business performance and continuing to execute effectively on all of the most important fronts. The second one is about sustaining our leadership position in immuno-oncology. Third one is continuing to diversify the company for long-term growth. And finally business development and capital allocation remain really important.
Let me just spend a few minutes now to discuss the way I think about our immuno-oncology opportunities here. As I have mentioned over the last couple of months, I really see three elements of our IO priorities and portfolio this year. The first one is our U.S. business in lung cancer, obviously there has been a lot of discussion about lung cancer, Steve referenced some of that in his introduction. And it is clear that why we have been extremely successful with Opdivo in establishing Opdivo as the standard of care in second-line lung cancer.
The clinical developments of the last eight months have somewhat transformed the landscape in lung. And so I do see that market as one that in the short-term is very competitive, particularly in the U.S. with the entry of Keytruda in a small segment of the first-line in monotherapy. The pending application for Keytruda in combination with chemotherapy in first-line lung cancer and obviously more approvals in second-line. So, that is a segment of our business, where we are working to defend our leadership position in second-line, but clearly in the short-term a very competitive market.
In the U.S. ex-lung, there continues to be strong momentum in our business. We see good performance in melanoma, primarily with our combination regiment of Opdivo and Yervoy. We see very strong performance in renal, where in second-line we continue to gain market share. We have good performance across the board with more recent launches in Hodgkin Lymphoma head and neck cancer and bladder.
So, the rest of our business actually is in very, very good position competitively and continuing to grow in the U.S. And internationally, we have been very successful with negotiating pricing and reimbursement across the world. I must say that that process is completed in a vast majority of international markets. In many cases, we are at the beginning of uptake launches and curves that look very similar to what we have seen in the U.S. one or two years ago.
With strong competitive position in many key markets, like Germany, France, Italy, Spain to mention some of the European markets. And all actually of the key markets around the world. So the dynamics of this business will be very different, depending on which one of the three buckets we discuss.
Overall, we have guided to our overall immuno-oncology business to grow this year versus last year as a whole and internationally. Obviously the competitive position is more intense in the U.S. and as we said, while our business in the U.S. can also grow this year, a lot depends on the evolution of market dynamics.
Let me now switch and very briefly touch on what has now evolved to be our program in first-line lung cancer. And as the slide describes, our program is extremely broad, we have an opportunity to study 227 and 568 to be really either in Phase III with 227 or potentially into a registrational study with 568. And test in parallel multiple hypothesis clearly at the center of our strategy remains the potential of the I-O combination of Opdivo and Yervoy.
But we have the opportunity to look at the combination of Opdivo in chemotherapy not only in period one negative patients, but actually in all comer population as well. And we are beginning to test what I think is a really interesting hypothesis to initiate Opdivo and Yervoy in parallel with two cycles of chemotherapy. And then after the two cycles continue the I-O regimen as a potential strategy to address the needs of rapidly progressing patient.
This is a broad programs probably the broadest in the industry and obviously at BMS we are extremely focused with all of our resources to ensure this program is well executed and executed on time.
Beyond first line lung cancer, our lung cancer strategy is also very broad. You see here some of the studies that led to broad approvals in second line, you see a reference to study 227 and 568 in first line lung cancer. We are also studying the potential for adjuvant and neoadjuvant studies in lung cancer, which we think is extremely important. And particularly with respect to the neoadjuvant setting there is data that suggests really important role for Opdivo as a neoadjuvant strategy in lung cancer.
While there is a lot of focus on lung cancer, we are not only a lung cancer company. As I mentioned Opdivo and Yervoy are being studied in a large number of clinical trials. There is at least a dozen clinical programs that could lead to registrational paths over the next two years. And you see some of them listed in this slide with the dates in which we expect to have data that could lead to registrational submission.
Moving to longer term, let me now spend just a couple of minutes to describe our early pipeline in immune-oncology there are currently 10 new medicines in early stages of clinical development just in immune-oncology. And we are very excited actually to have probably the broadest and best pipeline we've ever had in oncology as a company.
Obviously, we decided even within immune-oncology to broaden our scope and this slide tries really to depict the four pillars of our immune-oncology strategy today. And the way we look at addressing different points of attack and different mechanisms of action as a company.
The slide also describes primarily our internal pipeline, and obviously as a company we have an opportunity to study many of the combinations that make sense in immune-oncology by leveraging our internal assets, which provides a great opportunity for speed and flexibility. But our strategy is not limited to using our own internal assets.
We are also growing a thoroughly comprehensive clinical collaboration strategy with multiple companies. And exploring the combination of our own products with targeted therapies, chemotherapy and a number of other approaches such as radiation therapy.
There are disclosures that will begin to be made on our early pipeline during the course of this year. As we have mentioned before many of our early programs are progressing quite well. There are at least four of those programs and in the next 12 months can generate data which could lead if positive to the beginning of registrational studies.
You see here some of the data we intend to present in the first part of this year. And then potential for disclosures in the second part of 2017 on a number of really interesting programs.
The other area that I want to cover is really the area of biomarkers and patient segmentation. It is clear to us that while the first chapter of immune-oncology really has led to the establishment of Opdivo as a foundational medicine in cancer, and demonstrated the value of Opdivo in combination with the Yervoy in a number of tumor types. The future is one where multiple mechanisms of action may be combined and clearly one where also different lines of therapy need to be developed for patients across multiple tumors.
And it is therefore essential that as a company we continue to strengthen our science and translational medicine capabilities, the ability to identify biomarkers and segmentation strategies as a company. We've already invested very significantly in this space, but it is an area in which I expect you will continue to see activity at Bristol-Myers Squibb. Because clearly as a company that has such a rich pipeline, it is essential for us to continue to be at the forefront in this area as well.
You see some of the agreements with third parties on this slide. This is only part of the story, the other part of the story is clearly a strong partnership with the academic community. Several years ago, we made a decision to create what we call the internally immuno-oncology network, which is a really close network that brings together I would say approximately 15 of the leading academic institutions around the world active in immuno-oncology.
And with every one of them we have a close partnership and calibration in order to continue to generate the data that enables to us to understand how to take our programs forward. So, within oncology, this is clearly an area that will continue to receive significant attention from our perspective.
Let me just now mention in a few words what’s happening outside of oncology. And as you may remember, we decided to focus strategically our efforts in three areas outside of oncology. One is cardiovascular medicine, the other one immunoscience and the third one fibrotic diseases. They are all areas in which we have expertise either clinical assets or growing critical mass or clinical programs in general.
I’ll just point to some of the Phase II programs there. Nitroxyl Donor in heart failure, three programs in immunoscience and a number of program in fibrotic diseases. I think these are all areas where our programs continue to advance. Outside of oncology as I said earlier we do an opportunity for four of our programs to generate data in the next 12 months, which could lead to registrational programs. And I’ll also point to maybe the first disclosure coming, which is the release of interesting early data on one of our assets in fibroses Adesol [ph], later in April.
As I’ve mentioned a number of times, business development remains a critical priority for the company. In fact we are sized and we are strategically focused on considering business development as an important source of innovation for the company, which compliments internal R&D effort. You see examples of some of the things that we’ve done over the last few years. There clearly is a focus on oncology, but you’ll see that quite a lot has happened to strengthen our pipeline outside of oncology.
So in closing, let me just say that there is strong momentum in the company. We are coming out of 2016 which has been a year of extremely solid commercial execution, the company has grown 17% in sales, 40% in earnings. We have strengthened and broadened our development strategy in lung cancer specifically with respect to Opdivo and the combination of Opdivo with Yervoy. We have a dozen catalysts for the medium term -- short and medium term that can broaden further the development -- the approval of Opdivo and Yervoy in a number of tumor types.
And in the long-term we are making bright progress to advance an extraordinary promising pipeline in oncology and a select number of therapeutic areas. We are continuing to maintain a balanced capital allocations strategy and we are well resourced from a financial perspective and talent perspective to execute on our strategy. Thank you. Steve?
Question-and-Answer Session
End of Q&A
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http://seekingalpha.com/article/4052464-bristol-myers-squibb-bmy-ceo-giovanni-caforio-presents-cowen-company-37th-annual-health-care?part=single
BMY
I generally don't post when I have no shares in a stock (although I look to buy back in), but you may be correct The volume that day was relatively low compared to the surrounding days. Sure has been an uptick in volume the last 6 trading days compared to prior days:
Results for: 3 Month, From 03-DEC-2016 TO 03-MAR-2017
Date Open High Low Close / Last Volume
16:00 2 2.09 1.945 1.99 1,807,088
03/03/2017 2 2.09 1.945 1.99 1,807,007
03/02/2017 1.88 2.1 1.84 2.04 3,415,509
03/01/2017 1.93 1.94 1.81 1.87 1,833,366
02/28/2017 1.7 1.945 1.6815 1.87 4,255,698
02/27/2017 1.67 1.7 1.63 1.65 1,842,253
02/24/2017 1.72 1.76 1.63 1.67 1,494,119
02/23/2017 1.7 1.73 1.67 1.73 814,169
02/22/2017 1.65 1.73 1.64 1.68 808,221
02/21/2017 1.76 1.77 1.63 1.66 1,048,529
02/17/2017 1.68 1.79 1.655 1.74 1,217,306
02/16/2017 1.68 1.71 1.63 1.68 964,281
02/15/2017 1.58 1.68 1.58 1.67 998,196
02/14/2017 1.58 1.61 1.56 1.58 470,289
Read more: http://www.nasdaq.com/symbol/idra/historical#ixzz4aY7YW0t3
IDRA
I see approximately 6000 additional shares, not 1,594,741. Why wouldn't the seller hold on for dividends. Maybe BMY was doing their buyback on this one?
16:00:27 $ 57.26 570
16:00:27 $ 57.26 166
16:00:27 $ 57.26 916
16:00:27 $ 57.26 1,164
16:00:27 $ 57.26 285
16:00:27 $ 57.26 1,407
16:00:27 $ 57.26 100
16:00:27 $ 57.26 198
16:00:27 $ 57.26 90
16:00:27 $ 57.26 1,000,000
16:00:27 $ 57.26 190
16:00:27 $ 57.26 91
16:00:27 $ 57.26 8
16:00:27 $ 57.26 583
16:00:27 $ 57.26 340
Read more: http://www.nasdaq.com/symbol/bmy/after-hours#ixzz4aY34IKvL
BMY
Quite a trade AH:
16:00:27 $ 57.26 1,000,000
http://www.nasdaq.com/symbol/bmy/after-hours
BMY