Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
If you'll be in Chicago or at ASCO 2012, make sure to come by Adam Feuerstein's Tweetup on Friday night. See link for details - http://www.tweetvite.com/event/ascotweet
(I will be at the meeting; if anyone from the board will, feel free to PM me and we can meet up.)
Stock was up today because GSK/Pronova won in court vs. TEVA/Par over generic Lovaza. Apotex has a deal for a Q1'2015 launch
Mylan Launches Generic Version of Lipitor
I will have to dig thru the patent applications and talk with a biochem consultant before guessing on this. Need to see some previous case law as well.
Also noticed a former VRUS employee/inventor is suing GILD/VRUS. Guess he didnt get paid well enough in the buyout.
"In March 2012, Jeremy Clark, a former employee of Pharmasset, Inc. (Pharmasset), which we acquired in January 2012, and inventor of U.S. Patent No. 7,429,572, filed a demand for arbitration in his lawsuit against Pharmasset and Dr. Raymond Schinazi. Mr. Clark initially filed the lawsuit against Pharmasset and Dr. Schinazi in Alabama District Court in February 2008 seeking to void the assignment provision in his employment agreement and assert ownership of U.S. Patent No. 7,429,572, which claims metabolites of GS-7977 and RG7128. In December 2008, the court ordered a stay of the litigation pending the outcome of an arbitration proceeding required by Mr. Clark's employment agreement. Instead of proceeding with arbitration, Mr. Clark filed two additional lawsuits in September 2009 and June 2010, both of which were subsequently dismissed by the court. In September 2010, Mr. Clark filed a motion seeking reconsideration of the court's December 2008 order which was denied by the court. In December 2011, Mr. Clark filed a motion to appoint a special prosecutor. In February 2012, the Alabama court issued an order requiring Mr. Clark to enter arbitration or risk dismissal of his case. Mr. Clark filed a demand for arbitration in March 2012. We cannot predict the outcome of the arbitration. If Mr. Clark is ultimately found to be the owner of the 7,429,572 patent and it is determined that we have infringed the patent, we may be required to obtain a license from and pay royalties to Mr. Clark to commercialize GS-7977 and RG7128."
GILD's 10Q doesnt sound quite so bullish compared to the CFO's comments. Like I said, a tall order for the junior party(Gilead) to win in these cases.
-----------
"Our patent covers metabolites of GS-7977 and RG7128. Idenix is attempting to claim a class of compounds including these metabolites in their pending patent application. In the course of this proceeding, both parties will be called upon to submit evidence of the date they conceived of their respective inventions. The Interference will determine who was first to invent these compounds and therefore who is entitled to the patent claiming these compounds. If the administrative law judge determines Idenix is entitled to these patent claims and it is determined that we have infringed those claims, we may be required to obtain a license from, and pay royalties to, Idenix to commercialize GS-7977 and RG7128."
Hard to get very excited by the potential of some combos because costs will largely be prohibitive. Abraxane + Vismodegib would be a ridiculously expensive course of therapy.
Can you explain why GSK chose to use PFS as primary endpoints in both of their Phase 3 studies? Seems like they're taking a risk on OS not coming through, since I believe both trials were halted early.
Trametinib
http://abstract.asco.org/AbstView_114_96304.html
http://clinicaltrials.gov/ct2/show/NCT01245062?term=1120212&rank=15
Dabrafenib
http://clinicaltrials.gov/ct2/show/NCT01227889?term=GSK2118436+phase+III&rank=1
http://abstract.asco.org/AbstView_114_96291.html
re CRIS in data in pancreatic cancer thus far... Not optimal.
A phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): Interim analysis of a University of Chicago phase II consortium study.
Background: Sonic Hh (SHh), the ligand for the Hh pathway, is over-expressed in >80% of PC. V, a small molecule antagonist of the Hh signaling pathway, has activity in preclinical PC models. Methods: We conducted a multi-center, placebo-controlled, phase IB/randomized phase II trial of GV or GP. Eligible pts, KPS 80-100, had previously untreated metastatic PC, or had completed adjuvant therapy > 6 months (mo) prior. Primary endpoint: progression-free survival (PFS). Correlatives: serial SHh serum levels; serial contrast perfusion CT imaging. To allow for early stopping due to lack of efficacy, a planned interim analysis was performed after approximately 50% of the expected number of PFS events occurred. The protocol stipulated that the trial would be terminated if the probability of rejecting the null hypothesis were the trial to continue (conditional power) was <10%. All pts received G 1000mg/m2 over 30 minutes, days (D) 1, 8, 15, Q28D. Pts, stratified by KPS (80 v 90/100), and disease status (newly-diagnosed/recurrent), were randomized to V (150 mg PO daily) or P. For pts on P, cross-over was allowed at progression.
Results: 70 evaluable pts (V/P 35/35) enrolled at 12 sites 2/10-6/11. Pt characteristics: median age 63/63 (range 49-79/48-82); KPS 80: 8/8; 90: 12/14; 100: 15/13. Grade 3/4 toxicity (%pts): neutropenia 20/26; hyponatremia 3/11; fatigue 9/6; hyperglycemia 14/6; elevated alkaline phosphatase 9/11. Response (%): complete 0/3, partial 0/11, stable disease 49/31. Median PFS: 3.7/2.4 mo (95% CI: 2.4-4.6/1.9-3.7; adjusted HR 0.92 [0.52-1.64]). Upon progression/unblinding, 23 GP pts crossed over to GV. Median overall survival (OS): 6.3/5.4 mo (95% CI:4.9-7.8/4.2-8.0, adjusted HR 0.97, [0.47-2.01]). 1-year survival (%): 24/24. Laboratory and radiological correlatives will be presented.
Conclusions: GV has an acceptable toxicity profile. This trial did not meet criteria for futility at this interim analysis. The study is expected to complete accrual of 112 pts in February 2012. The final analysis will be reported after 90 events. Funded by NCI N01-CM-62201.
http://abstract.asco.org/AbstView_114_98474.html
I always enjoy Alex's pieces, more so than any other biotech analyst. But yeah, he tends to use hyperbole a lot to get his point across.
Here I think he is somewhat right with his use of it because of how low CLDX's market cap is relative to the opportunity. Not saying it'll be huge like him, but $250mcap seems pretty low to me.
Are you claiming that they shouldnt test further in high GPNMB patients in this setting or at all? I still want to see more mature data in the current trial before rushing to judgement.
If the latter, I'd say its presumptuous to kill it in the high GPNMB group without looking at the drug in a bit healthier group of patients.
Salvage setting also makes it hard to see the true potential of CDX-011.
I have been speaking with a PhD biochemist I know and he says that Idenix's patents broadly cover most of the PSI structures. The main question is who owns the core patent for nucleosides, not the metabolites. I dug around a little and indeed Idenix provisional applications date back to June 2002, over a year before Pharmasset patent in question. Since US is first to invent, it could come down to dated lab notebooks.
Idenix presumably has an upper hand because of the senior party designation. I've seen quotes stating the senior party wins in greater than 90% of these kind of cases. Not sure what Idenix gets though.
------------------------------------------------
Bank of America has published a research report on Idenix Pharmaceuticals (NASDAQ: IDIX) commenting on what to expect from settlement talks for the company.
In the report, Bank of America writes, "A document was recently posted providing an update on the patent interference between GILD and IDIX related to patent ‘572 covering GILD's HCV nuc GS-7977. The document notes that by law, parties within three months of a patent interference declaration must enter into settlement discussions; IDIX and GILD (B-1-9; US$50.62) have discussed the possibility of a settlement and plan additional discussions in June. Given the settlement discussions are court mandated, it is difficult to draw conclusions or assign probabilities on the outcome of such discussions. We currently assign $6/sh in our IDIX for potential royalties on future sales of GS-7977."
Bank of America maintains its Buy rating and $15 price objective on Idenix Pharmaceuticals, which closed yesterday at $10.08.
Read more: http://www.benzinga.com/analyst-ratings/analyst-color/12/05/2618942/bank-of-america-comments-on-settlement-talks-for-idenix-#ixzz1vw4wqKNB
I imagine its because the number of patients with greater than 50% expression levels was quite small or there was none in the control arm to compare against. Hard to know at this point. Data needs time to mature.
I will try and give management a call about this.
Does anyone understand why ECYT is trading below cash value?
I used a little bit of hyperbole, but I think the point is clear. Obviously CLDX doesnt/didnt have the cash/resources to run this the way it should have been, but its a good proof of concept study. It's randomized active-controlled data, which more than we can say about most data out there.
Agree with you that ORR is a poor endpoint. Actually Ixempra's Phase 2 trial illustrated this very point. Their single-arm Phase 2 trial in heavily pre-treated(prior A/T/C) breast cancer patients, IRF-assessed ORR was 11.5% but the investigator-assessed ORR was 18.3%, which is a 59% difference. Dr. Vahdat does disagree with on the ORR to PFS point, at least in this setting. Remember the PFS data they presented were not mature.
On your last point about the population size for the drug, I think it's much too early to say where CDX-011 could fit. This is the last-line setting, so I imagine if tested much earlier or in combo, we would be seeing drastically higher responses.
If you take CLDX's name out and put a mid/big cap pharmas, everyone would be claiming blockbuster. It's a good proof of concept study that gives them a path forward.
Medivation and Astellas Announce Submission of New Drug Application for Enzalutamide for the Treatment of Castration-Resistant Prostate Cancer in Patients Previously Treated With Chemotherapy
SAN FRANCISCO, CA and TOKYO--(Marketwire -05/21/12)- Medivation, Inc. (MDVN) and Astellas Pharma Inc. (Tokyo:4503) announced that Medivation has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for enzalutamide (formerly MDV3100). The compound has been studied in patients with castration-resistant prostate cancer who have received docetaxel therapy.
Pursuant to the Prescription Drug User Fee Act (PDUFA), the FDA is expected to determine within 60 days whether to accept the filing for review. Medivation has requested Priority Review, a designation given to drugs that offer a significant improvement in treatment or provide treatment where no satisfactory alternative therapy exists. If a Priority Review is granted, the FDA goal for completing a review is six months.
About Enzalutamide (formerly MDV3100)
Enzalutamide is an oral, once-daily investigational agent that is an androgen receptor signaling inhibitor. Enzalutamide inhibits androgen receptor signaling in three distinct ways: it inhibits 1) testosterone binding to androgen receptors; 2) nuclear translocation of androgen receptors; and 3) DNA binding and activation by androgen receptors.
In the Phase 3 AFFIRM trial, enzalutamide was well tolerated. Common side effects observed more frequently in enzalutamide as compared with placebo-treated patients included fatigue, diarrhea and hot flush. Seizure was reported in < 1% of enzalutamide-treated patients. Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death all were lower in the enzalutamide group than in the placebo group.
Unless they follow through on a better accelerated approval pathway, I dont see the new PDUFA as a net positive for small/mid caps going thru development.
I am happy that CLDX ran the trial at only US sites and that the principal investigator, Dr. Vahdat, is a fairly well-established breast cancer oncologist. Success in their trial depends on a few variables
- Whether CDX-011 actually hits GPNMB well enough to produce enough of an effect. If it does, the GPNMB screening should help boost ORR. (Obviously a big one)
- What the control arm is going to look like. ORR can be highly variable in Ph2, especially b/c of no independent review
- Patient baseline values(specifically prior # of anticancer regimens) will make a big impact on ORR
Under the inclusion criteria, it says "Unless not a candidate for these agents, prior therapies must have included a taxane, an anthracycline, and capecitabine, as well as trastuzumab and lapatinib for patients whose tumors are positive for the human epidermal growth factor receptor 2 (HER2). (Patients who received incomplete courses of therapy with these agents due to intolerance will be eligible.)"
Wouldnt that imply most patients would have received 3 prior therapies?
http://clinicaltrials.gov/ct2/show/study/NCT01156753?term=cdx-011&rank=1&show_locs=Y#locn
man the general market situation has really soured your grapes
In context of the KRAS subpopulation of NSCLC, it is very good data. Sorry if the use of the word 'great' made it come off too strong. Comparatively, no other trial has come close(net delta) to what was been seen in this trial for KRAS. It'll be interesting to see SNTA's subgroup data here.
There are some statistical nuances, but I think it is worth noting that those are likely the fault of AZN switching the primary endpoint from PFS to OS midway through the trial without adding more patients to the trial.
"Abstract 6507: Single-agent ibrutinib showed a 73% ORR (65% PR 8% CR) in elderly (71 years 65-84) treatment naive patients with CLL at 10.7 months median follow-up."
This data is even more impressive when you consider 74% were older than 70.
GSK's BRAF and MEK inhibitor abstracts can be found here
http://abstract.asco.org/AbstView_114_96291.html
http://abstract.asco.org/AbstView_114_97727.html
http://abstract.asco.org/AbstView_114_98045.html
http://abstract.asco.org/AbstView_114_96304.html
http://abstract.asco.org/AbstView_114_101227.html
I dont see it as feasible anyways. Cost would be too prohibitive.
Try here
http://abstract.asco.org/ConfCatView_114_S.html
Or are you looking for something else?
Efficacy and safety of oral MEK162 in patients with locally advanced and unresectable or metastatic cutaneous melanoma harboring BRAFV600 or NRAS mutations.
Background: BRAF and NRAS mutations occur in 50-60% and 15-20% of cutaneous melanomas, respectively. MEK162, a selective inhibitor of the kinases MEK1 and MEK2, has shown pre-clinical activity in BRAF and NRAS mutant (mt) melanoma models. This open label, phase II study assessed the antitumor activity of MEK162 in patients (pts) with BRAFV600 and NRAS mt advanced cutaneous melanoma. Methods: MEK162 was administered orally at a starting dose of 45 mg twice daily. Treatment was until unacceptable toxicity, disease progression (PD) or investigator or patient refusal. Tumor response was assessed by CT imaging every 8 weeks (RECIST 1.0) until PD.
Results: As of 16 Sept 2011, the full analysis and safety populations comprised 66 pts: 42 BRAF mt and 24 NRAS mt. Median age 58.0 years; 57.6% male; 72.7% WHO performance status 0. All NRAS pts and all but 2 BRAF (1 each stage IIIB and IIIC) pts had stage IV disease, and 87.5% of NRAS pts and 66.7% of BRAF pts had received prior therapy at study entry. Median time from 1st diagnosis to 1st dose of drug was 40.4 months. Median time on study was 10.4 and 8.5 weeks for the BRAF and NRAS arms. Relative dose intensities of 80–<100% were received by 71.4% and 70.8% of pts, respectively.
Among 29 BRAF mt and 13 NRAS mt pts evaluable for efficacy, 1 confirmed and 6 unconfirmed partial responses (PRs) and 9 pts with stable disease (SD) were recorded in the BRAF arm and 2 confirmed PRs, 1 unconfirmed PR and 4 pts with SD recorded in the NRAS arm.
Common treatment–related adverse events (AEs), all grades (Gs) and all pts, were rash (40.9%), diarrhea (33.3%), acneiform dermatitis (27.3%), creatine phosphokinase (CK) elevation (25.8%), fatigue (18.2%) and peripheral edema (21.2%). Central serous retinopathy-like retinal events (G 1/2 only) were reported in 8 (12.1%) pts (6 G1, 2 G2). All retinal events were reversible. G3/4 AEs in >1pt were diarrhea (4.5%) and CK elevation (15.2%). 5 pts discontinued due to toxicity. 34 pts are ongoing with more responses under current review.
Conclusions: MEK162 showed clinical activity and good tolerability in pts with BRAF and NRAS mt advanced melanoma. This is the 1st targeted therapy to show activity in pts with NRAS mt melanoma.
Blowout data from ARRY(in my opinion)
Phase II double-blind, randomized study of selumetinib (SEL) plus docetaxel (DOC) versus DOC plus placebo as second-line treatment for advanced KRAS mutant non-small cell lung cancer (NSCLC).
Background: KRAS mutations are the most common (~20%) oncogenic alteration in NSCLC. There are no effective targeted therapies for this subset of NSCLC. Selumetinib (AZD6244, ARRY-142866) inhibits MEK1/2 signaling downstream of KRAS. We prospectively evaluated SEL + DOC vs DOC + placebo in advanced KRAS mutant NSCLC based on preclinical observations (NCT00890825). Methods: Patients (pts) with stage IIIB-IV, KRAS mutant NSCLC, who had received prior chemotherapy, received iv DOC 75 mg/m2, and po SEL 75 mg or placebo BD. The primary endpoint was overall survival (OS); secondary endpoints included: progression-free survival (PFS), objective response rate (RR), duration of response, change in tumor size, proportion of patients alive and progression-free at 6 mo, and safety and tolerability.
Results: Between April 2009 and June 2010, 422 pts were screened across 67 centers in 12 countries; 113 had KRAS mutant NSCLC and 87 were randomized (DOC, 43; SEL/DOC, 44). Baseline characteristics were balanced (DOC vs SEL/DOC): WHO PS 0, 49%/48%; Female, 54%/52%; KRAS codon 12, 90%/93%. Median number of cycles: DOC, 4; SEL/DOC, 5. Most frequent grade 3/4 hematologic toxicity (DOC vs SEL/DOC): neutropenia (54.8%/67.4%), febrile neutropenia (0%/15.9%); most frequent grade 3/4 non-hematologic toxicity: dyspnea (11.9%/2.3%) asthenia (0%/9.1%), respiratory failure (4.8%/6.8%), acneiform dermatitis (0%/6.8%). Discontinuation due to AEs was similar: 18.2% SEL/DOC vs 11.9% DOC.
OS was longer for SEL/DOC vs DOC (9.4 mo vs 5.2 mo; 56 events, median follow-up 219 days) but did not reach statistical significance; hazards were non proportional (HR 0.80; 80% CI 0.56, 1.14; 1-sided p=0.2069). All secondary endpoints, including RR (DOC 0%, SEL/DOC 37%; p<0.0001) and PFS (DOC 2.1 mo, SEL/DOC 5.3 mo; 71 events; HR = 0.58; 80% CI 0.42, 0.79; 1-sided p=0.0138), were significantly improved for SEL/DOC vs DOC.
Conclusions: This is the first prospective study to demonstrate a clinical benefit of a targeted therapy (SEL + DOC) for patients with KRAS mutant cancer of any type. Our findings could have implications for the treatment of NSCLC and other KRAS mutant cancers.
Really impressive ASCO data out of EXEL PCYC and ARRY
IMPORTANT! Here is link to a file w/ 50 #ASCO12 abstracts. Most/all impt stuff. Enjoy! --> http://bit.ly/KgnrJG #biotech $$
My story summarizing the newsworthy data from #ASCO12 abstract data dump --> http://bit.ly/Kgphdx I would appreciate the page views.
Adam Feuerstein ?@adamfeuerstein
Agree. Everyone harping about CRPC, when the drug is likely to be used in multiple indications. Combo of it and MDV3100 would be real interesting, esp. in bone mets.
Dont think they mean partner in the sense of a licensing deal. Think they mean partner with a CRO to run the trial.
Celldex open to partnering with CRO to run 400- to 500-patient Phase III breast cancer trial, CMO says
2012-05-10 BioPharm Insight
Celldex Therapeutics (NASDAQ: CLDX) is open to partnering with a clinical research organization (CRO) on a Phase III trial of its resistant GPNMB-expressing breast cancer candidate CDX-011, chief medical officer Thomas Davis said.
Given the complexity of a Phase III breast cancer trial and the competitiveness of the market, the Needham, Massachusetts-based biopharmaceutical company is open to discussions with companies other than the unnamed US-based CRO contracted for its Phase IIb trial, Davis said. However, it is not yet ready to formally commit to a particular CRO.
The desired level of CRO involvement in the Phase III study will depend on whether the trial will be conducted in North America or globally. That decision will be based on the outcome of the Phase IIb trial — which is studying the drug in advanced breast cancer — and on negotiations with the Food and Drug Administration (FDA), Davis said.
He noted the company already contracts CROs to perform functions such as data and site management and potentially even statistics work. However, responsibility for running an entire trial depends on the nature of the study.
According to Davis, Celldex can manage patient enrollment within the US, but would delegate responsibilities to a CRO if the Phase III trial is conducted globally.
The Phase III trial would not start for another six to nine months and would require discussing its design with the FDA, Davis said. It will likely be designed to compare CDX-011 against an "investigator's choice chemotherapy," the same design as the Phase IIb trial but in a larger population — approximately 400 to 500 patients. It may also test CDX-011 as a single-agent in the early-stage breast cancer setting.
After a technical glitch that prevented it from presenting an abstract at the American Society of Clinical Oncology's upcoming annual meeting in June, Celldex will instead present top-line results from the Phase IIb study in a webcast on 23 May.
If data from that study show significant duration of response, Celldex plans to discuss accelerated approval with the FDA after the Phase IIb results have been finalized, which will take around three months. The company would use objective-response rate data as a surrogate endpoint.
An FDA decision in favor of accelerated approval would require Celldex to perform a large, randomized Phase III trial evaluating overall survival in order to gain marketing approval.
The drug maker aims to present final Phase IIb data for CDX-011 at the San Antonio Breast Cancer Symposium in December 2012, but cannot guarantee that the data will be ready then or even in early 2013, Davis said.
CDX-011 is an antibody conjugate that targets glycoprotein NMB (GPNMB), which is overexpressed in approximately 50% of all breast cancer patients. Delivered intravenously, the drug is designed to affect cells in which GPNMB is overexpressed.
Licensing and M&A
Davis said Celldex continues to engage in "active" licensing discussions for CDX-011 and aims to find a partner ahead of the Phase III trial. However, the company would not delay the study if it is unable to find a partner in time, he said.
Describing another candidate, Davis said the company is not actively seeking partners for its glioblastoma vaccine rindopepimut, which is currently being assessed in a Phase III trial in newly diagnosed glioblastoma. Celldex would not need a partner for a North American study, though it is open to a rest-of-world partner, he said.
Celldex regained full worldwide rights to develop and commercialize rindopepimut from Pfizer (NYSE: PFE) in November 2010.
In February, Celldex raised USD 37.7m in a public offering. Although being acquired is not currently part of Celldex's corporate strategy, Davis acknowledged that smaller drug makers today are rarely able to carry a drug through to market approval.
Celldex has a market cap of USD 237.3m.
by Juliana Wexler and Anusha Kambhampaty in New York
VRTX Kalydeco approval related documents here
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188s000TOC.cfm
Isn't that the drug similar to Anthera's which failed recently?
Multiple Revlimid papers in NEJM
Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma - Continuous lenalidomide after MPR improved progress-free survival by 31 mos in transplant-ineligible mult myeloma pts.
http://www.nejm.org/doi/full/10.1056/NEJMoa1112704
Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma - Lenalidomide maintenance for mult myeloma after transplant signif improves progression-free, event-free survival.
http://www.nejm.org/doi/full/10.1056/NEJMoa1114138
Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma - Lenalidomide for myeloma post-transplant: More toxicity, 2nd cancers, but slower progression, better overall survival.
http://www.nejm.org/doi/full/10.1056/NEJMoa1114083
Not surprised to see ILNS and PSTI listed there. Definitely pump/dumps.
DNDN Q1 Provenge sales $82M, 1Q Loss $103.9M (-$0.59/share), gross margin 26.8% (ouch).
FDA Drug Safety Communication: Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies
This update is in follow-up to the FDA Drug Safety Communication: Ongoing safety review of Revlimid (lenalidomide) and possible increased risk of developing new malignancies.
http://www.fda.gov/Drugs/DrugSafety/ucm250575.htm
[5-07-2012] The U.S. Food and Drug Administration (FDA) is informing the public of an increased risk of second primary malignancies (new types of cancer) in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide). Clinical trials conducted after Revlimid was approved showed that newly-diagnosed patients treated with Revlimid had an increased risk of developing second primary malignancies compared to similar patients who received a placebo. Specifically, these trials showed there was an increased risk of developing acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma.
This safety information has been added to the Warnings and Precautions section of the Revlimid drug label. The patient Medication Guide is also being updated to inform patients about this risk.
Healthcare professionals should consider both the potential benefit of Revlimid and the risk of second primary malignancies when deciding to treat patients with this drug, and monitor patients for this risk.
Patients should contact their healthcare professional if they have any questions or concerns about Revlimid.
In April 2011, FDA announced an ongoing safety review to evaluate the possible increased risk of second primary malignancies with Revlimid. FDA performed a comprehensive review of this safety issue (see Data Summary below).
Additional Information for Patients
Know that, in clinical trials of patients newly diagnosed with multiple myeloma, those patients treated with Revlimid had an increased risk of developing new cancers, particularly, acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma, compared to patients receiving a placebo.
Additional Information for Healthcare Professionals
Know that, in clinical trials of patients newly diagnosed with multiple myeloma, those patients treated with Revlimid had an increased risk of developing second primary malignancies, particularly, acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma, compared to patients receiving a placebo.
Monitor patients taking Revlimid for the development of second primary malignancies.
Take into account both the potential benefit of Revlimid and the risk of second primary malignancies when considering treatment with Revlimid.
Encourage patients to read the Medication Guide when they receive their Revlimid prescription.
Please continue to report adverse events involving Revlimid to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
Data Summary
FDA reviewed controlled clinical trials of Revlimid as maintenance therapy in patients with newly-diagnosed multiple myeloma and for the treatment of relapsed/refractory multiple myeloma, to evaluate the risk of developing a second primary malignancy with Revlimid.
Second primary malignancies in patients with newly diagnosed multiple myeloma
In three prospective, randomized trials, patients with newly-diagnosed multiple myeloma received initial chemotherapy or chemotherapy plus blood stem cell transplantation followed by treatment with Revlimid or a placebo. This treatment protocol was used to study the effect of Revlimid as maintenance therapy. A pooled analysis of the three ongoing trials, as of February 28, 2011, showed 65 second primary malignancies among 824 patients in the Revlimid treatment arms compared to 19 second primary malignancies among 665 patients in the treatment arms that did not include Revlimid maintenance (7.9% vs. 2.8%; p<0.001). This difference is almost a three-fold increase in new malignancies for the groups receiving Revlimid versus the groups that did not receive Revlimid. The second primary malignancies noted included acute myelogenous leukemia (AML), myelodysplastic syndromes (MDS), and B-cell malignancies. Overall, 30 (3.6%) second primary hematologic malignancies were reported in the Revlimid treatment arms (22 MDS/AML, 5 Hodgkin lymphoma, 3 B-cell acute lymphoblastic leukemia) compared with 2 (0.3%) cases of AML in the study arms not receiving Revlimid. The median time from start of Revlimid to a diagnosis of a second primary malignancy was two years. Based on the available data, there appears to be no difference in the incidence of non-melanoma skin cancers or of solid tumors between the patients who received Revlimid and those who did not.
Second primary malignancies in patients with relapsed/refractory multiple myeloma
A retrospective pooled analysis of second primary malignancies also was conducted on data derived from the two clinical trials that supported the initial FDA approval for relapsed multiple myeloma. These were multicenter, double-blind, placebo-controlled, parallel-group trials of Revlimid plus high-dose dexamethasone therapy versus dexamethasone alone in the treatment of patients with relapsed or refractory multiple myeloma. The incidence rates of developing a second primary malignancy during the treatment phase of these trials were 3.98 and 1.38 per 100 person-years for patients in the Revlimid/dexamethasone and the placebo/dexamethasone groups, respectively. The higher incidence rate of second primary malignancies in the Revlimid/dexamethasone group was largely accounted for by the higher incidence of non-melanoma skin cancers with Revlimid (2.4 vs. 0.91 per 100 person-years for the Revlimid/dexamethasone and placebo/dexamethasone groups, respectively). The patients in the Revlimid/dexamethasone group had longer on-study treatment time compared to the placebo/dexamethasone group (467 person-years vs. 218.7 person-years, respectively). When adjusted for the differences in observation time on-study, the incidence rate of invasive non-melanoma skin cancers was not substantially different between the two groups (1.71 vs. 0.91 per 100 person-years, respectively).
Isn't the 5% improvement in FEV1 a little small?
Also need some longer term data to really know the sales potential.