Replies to post #120655 on Biotech Values

[DewDiligence]

JNJ’s own summary of its Investor Day webcast yesterday:

http://www.jnj.com/connect/pdf/publications-pdf/pharmaceutical-segment-review-highlights-backgrounder.pdf

›2011 Pharmaceutical Segment Review

May 26, 2011

In 2010, Johnson & Johnson invested $4.4 billion on pharmaceuticals research and development focused on five therapeutic areas. What follows is a summary of these therapeutic areas, including currently marketed products and late-stage development compounds.


Neuroscience -- We have a dedicated and longstanding commitment to neuroscience. Our research and development work is focused on neurology, which includes Alzheimer’s disease; psychiatry, with an emphasis on schizophrenia and mood disorders; and pain, specifically chronic pain and neuropathic pain. We use state-of-the-art science to move from a “diagnose- and-treat” approach to a “predict-and-prevent” paradigm.

We have a robust product portfolio in neuroscience, including INVEGA® SUSTENNA®/XEPLION®, INVEGA®, RISPERDAL®, RISPERDAL® CONSTA®, NUCYNTA®, DURAGESIC®, CONCERTA®, TOPAMAX®, ULTRACET®, ULTRAM ER®, JURNISTA®, AXERT® and RAZADYNE®/REMINYL® ER. We also have major line extensions with INVEGA for schizoaffective disorder and schizophrenia in adolescents, and RISPERDAL CONSTA in bipolar disorder.

Working toward our goal to reduce the burden of neuropsychiatric diseases, we are in the midst of Phase 3 clinical studies with bapineuzumab, a potential first-in-class therapy for Alzheimer’s disease. We also have an every-three-month formulation of INVEGA SUSTENNA in development. In addition, FDA action for NUCYNTA ER for chronic pain is pending, and we have a planned FDA filing for this agent for the treatment of diabetic peripheral neuropathic pain. We are also in Phase 2 of research for new non-opioid pain medicines with novel mechanisms of action.


Cardiovascular Disease and Metabolism – We are focused on the growing need for new treatment options that address the underpinnings of cardiovascular and metabolic conditions to improve outcomes for patients.

Our novel oral anticoagulant, rivaroxaban, has met or exceeded the primary efficacy endpoints in all eight of the phase 3 clinical studies reported to date. We have submitted two NDAs from this development program to the FDA seeking approval to use rivaroxaban to the prevent strokes in patients with atrial fibrillation, which is the most common sustained cardiac rhythm disorder, affecting 2.3 million people in the U.S. The other application seeks approval to use rivaroxaban to prevent the most common cause of re-hospitalization following total knee or hip replacement surgeries–venous thromboembolism. [Note the absence of any comment about submitting an NDA for the immobilized-patient indication tested in the MAGELLAN study (#msg-61803303).]

Two further large scale Phase 3 trials of rivaroxaban are expected to complete later this year. One will determine if rivaroxaban dosed in addition to standard of care can better protect patients with Acute Coronary Syndromes, and another for the treatment and prevention of recurrent deep vein thrombosis and pulmonary embolism events, is evaluating rivaroxaban against warfarin.

Canagliflozin, an oral SGLT2 inhibitor, is our lead agent for type-2 diabetes, a condition which affects 285 million people worldwide, according to World Diabetes Foundation estimates. We plan to submit for regulatory approval in the US and EU in the first half of 2012.

NOTE: Rivaroxaban developed in collaboration with Bayer Heatlth Care; Canagliflozin developed in collaboration with Mitsubishi- Tanabe Pharmaceutical


Immunology -- Our Immunology Therapeutic Area (TA) has a strong history of innovation in monoclonal antibody therapeutics with REMICADE® (infliximab), SIMPONI® (golimumab) and STELARA® (ustekinumab), and continues to build a pipeline of new biologic products, like sirukumab, an investigational compound being studied for rheumatoid arthritis (RA) and lupus nephritis. We are also expanding into small-molecule oral medications and broadening our disease focus in autoimmune, inflammatory and pulmonary diseases. And with the acquisition of RespiVert announced in June 2010, the Immunology TA strengthened its pulmonary capabilities with the addition of an expert scientific team and potential for a new class of inhaled medicines.

In addition, we have a broad biomarker discovery program that should further the understanding of disease pathogenesis, or how a disease develops and progresses. We are also developing co-diagnostics to predict a patient’s response to a drug in advance of treatment, therefore enabling better outcomes for patients.

We have established our leadership in Immunology through the development of innovative therapeutics that are focused on immune-mediated diseases with significant unmet needs such as inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, (RA), ankylosing spondylitis, psoriatic arthritis and psoriasis. An estimated 1 in 6 people in the U.S. suffer from such chronic immune-mediated diseases, each of which can be debilitating and result in serious co-morbidities, while negatively impacting an individual’s quality of life and ability to function.

REMICADE, the leading anti-tumor necrosis factor (TNF)-alpha therapy with 15 FDA approvals has been used to treat more than 1.5 million patients worldwide. Recognized as a “pipeline in a product,” REMICADE continues to be a well-established therapeutic option across a broad spectrum of immune-mediated diseases in such areas as gastroenterology, rheumatology and dermatology. In addition, applications seeking the approval of REMICADE for the treatment of pediatric ulcerative colitis are under review in the U.S. and Europe. Under the terms of an amended distribution agreement with Merck announced on April 15, 2011, distribution rights to REMICADE and SIMPONI in approximately 150 territories including Canada, Central and South America, the Middle East, Africa and Asia Pacific will be relinquished to Janssen companies on July 1, 2011.

SIMPONI, a human monoclonal antibody, is the first once-monthly subcutaneous anti-TNF- alpha therapy to be approved simultaneously for the treatment of moderately to severely active RA, active psoriatic arthritis and active ankylosing spondylitis. SIMPONI is also in a Phase 3 study as an intravenous formulation for RA, a Phase 3 study for the treatment of ulcerative colitis and Juvenile Idiopathic Arthritis, and is in a Phase 2 study for the treatment of sarcoidosis.

STELARA is a human monoclonal antibody that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are believed to play a role in the development of psoriasis. STELARA is indicated for the treatment of moderately to severely active plaque psoriasis. STELARA is administered via subcutaneous injection at weeks 0 and 4 and then every 12 weeks as a quarterly maintenance regimen. STELARA is currently in Phase 3 study for the treatment of psoriatic arthritis, Phase 2b study for the treatment of Crohn’s disease, and Phase 2 study for the treatment of sarcoidosis. STELARA is also entering Phase 2 study for the treatment of Primary Biliary Cirrhosis, an autoimmune disease affecting the bile duct with high morbidity and mortality due to liver failures.


Oncology -- Our oncology therapeutic area is focused on transforming cancer to a preventable, chronic or curable disease by delivering extraordinary and accessible diagnostic and therapeutic solutions that prolong and improve patients’ lives. Our strategy revolves around an intense focus on key cancer types through our tumor strategy groups, a deep understanding of the tumor microenvironment and a focus on intercepting cancer as it evolves from premalignancies to metastatic disease. Biomarkers are a key element of our approach, and all our oncology development programs have companion diagnostics in development as well.

Key products include the recently FDA-approved ZYTIGA™ (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel; VELCADE® (bortezomib), a treatment for multiple myeloma for which we have rights outside the US; and siltuximab (CNTO 328), which is in late stage development for Castleman’s Disease and multiple myeloma and is also being studied for smoldering myeloma, prostate cancer, Muscular Dystrophy Syndrome and anemia. In 2010, we attained rights to bendamustine in Latin America and parts of Asia; we plan regulatory filings in non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.


Infectious Diseases and Vaccines - Our infectious disease and vaccines therapeutic area is focused on the development of new HIV medications that are more potent, durable, convenient and tolerable. PREZISTA, our first marketed antiretroviral, is today the protease inhibitor (PI) of choice in Europe and the second most commonly used PI in the US. INTELENCE, is the only non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for use in treatment- experienced adult HIV patients with NNRTI-resistant virus. With the recent approval of EDURANT™, our second NNRTI, we are able to offer treatment naive adult patients a new once-daily option for use as part of HIV combination therapy. [See comments in #msg-63620130 re the pigeonholing of these two drugs.]

With more than 170 million people infected worldwide, hepatitis C virus (HCV) poses a significant burden on patients and society and one of the few viral infections that can be cured. The treatment paradigm for HCV is being transformed with the introduction of direct-acting antivirals for hepatitis C. Telaprevir, a HCV PI, has the potential to both substantially increase the success of HCV treatment as well as shortening its duration. It is now approved in the US where it is marketed by our partner Vertex. Our second HCV PI, TMC435 is being studied with once daily dosing in phase 3 regimen in both treatment naïve and prior treatment failure patients are now ongoing.

In 2009 an estimated 1.7 million people died of tuberculosis (TB), of particular concern is the increase in multi-drug resistant TB. That year, we entered into a R&D collaboration with the TB Global Alliance for the development of TMC207 which is potentially the first TB drug with a new mechanism of action in nearly 40 years; it is active against both drug susceptible and drug resistant TB. In addition to TB, we are moving more broadly into the field of viral respiratory infections such as influenza with the development of the monoclonal antibody FlumAb.

We have recently entered the field of prevention through the acquisition of Crucell. As a result we have a number of marketed vaccines and an exciting vaccine pipeline based on Crucell’s unique technologies, the PER.C6® cell line and the adenovector platform, and its experience in the field of virosomes formulation. It is through a combination of therapeutics and vaccines, small molecules and biologics that we will fight infectious diseases in the future thereby achieving our goal of saving lives and improving public health by worldwide.‹

[iandy]

>On JNJ’s Investor Day webcast yesterday, Husseini Manji (head of neuroscience) said the phase-2 Bapineuzumab data were reanalyzed by “eliminating the assumption of linearity,” and the reanalysis gave the company greater confidence that the phase-3 program will succeed. I’m not sure what he meant.<

I am guessing he was refering to a reanalysis of the data eliminating the outliers.

[masterlongevity]

In elan's primary analysis, they used a linear model to measure benefit of Bapineuzumab over PBO, insteead of calculating benefit on actual observed data. For some reason, they pre-specified the analysis would be done this way. Maybe because there are usually a lot of dropouts in AD trials.

For me, the remaining concern about bapi ph 2 data is this....

the average 18 mnth decline on ADAS-COG (gold standard for cognitive measurement) in hisotrical controls is about 8 points.

In the bapineuzumab carrier group, the bapi tx pts declined by 7.5 pts and the PBO declined by 8.5pts.

In the non-carrier group, the bapi tx pts declined by 7 pts and the PBO declined by 13pts.

Almost all of the benefit was do to a poorly perfroming PBO.

besides all that, i think the science is very good and makes good sense. i think bapi's chances in earlier AD or MCI would be better. There are a lot of dead neurons by the time patients have mild or moderate AD.