On September 16, 2010, an FDA Advisory Committee will review Alkermes application to extend the VIVITROL indication to include treatment of opioid abuse in addition to the alcohol dependency it currently has. When we first heard of this, we thought this was a slam dunk. Early indicators were that the clinical trial was statistically significant and the adverse event profile was not much different from what was seen with the patients who were being treated for alcohol dependency. But now we’ve seen the FDA Briefing document and things aren’t so clear. For one, the application is based on a single relatively small study conducted in Russia. In very guarded terms, the FDA has asked the Advisory Committee to determine if the study is applicable to the US patients. Why so? Because the patient population in the Russian study is very lean on people of color, only 2 Asians, the rest >99% are white. So, does it represent the patient population that will use the drug in the US? The short answer is NO. The “margin of efficacy” (our term, not theirs) is only a 12% difference in efficacy between the placebo patients and the Vivitrol treated patients. So, it is conceivable that if the drug is less effective in treating people of color then the “margin of efficacy” could disappear in a clinical trial population that represents the US patient population. And that we don’t know because Alkermes didn’t consider that in setting up the trial in Russia.
It is difficult to predict with any degree of accuracy how the Advisory Committee will go but the lack of data in a representative US patient population for whom the drug is intended is a major regulatory obstacle. If this study was done in the US, would the FDA accept the demographics? Probably not. Is this drug better than anything else that’s out there now for treating opioid dependency? Is it better than immediate release naltrexone for treating opioid dependency?
The FDA Advisory Committee will review Arena’s Lorqess (lorcaserin) on Sept 15, 2010 for the treatment of obesity. It’s hard to find anything positive to say about this. It looks like there’s still the marginal efficacy issue that was present before and the safety concerns, particularly regarding cardiovascular, are still there. Which means Arena has done little to increase the marginal benefit risk ratio they had before. The only question that remains unanswered is whether any of the Advisory Committee members will recommend approval.
The PDUFA Date for GILENIA (fingolimod) is September 21, 2010. This Novartis drug for the treatment of multiple sclerosis was reviewed by the FDA’s Advisory Committee in June of this year and received an overwhelmingly positive endorsement. There is little reason to believe that the FDA won’t be concurring with the Committee’s recommendation and approving this drug.
Another diet drug with cardiovascular problems, another Advisory Committee Meeting, only this time it’s not a case of getting the drug on the market. For drug maker Abbott, it’s a question of whether their data is strong enough to convince the Advisory Committee to recommend something other than withdrawal, one of 4 options the FDA has posed to the Committee. At the other end of the option spectrum of questions, the Committee could choose that the drug is safe, effective and the package insert as it is currently written is adequate. This is unlikely. Data suggests a cardiovascular problem and problems don’t go away if you keep doing the same thing. Ask Tiger Woods. Eventually you’re going to run into a tree.
We’ve said it before, obesity generally presents with co-morbidities of cardiovascular problems, diabetes, respiratory etc. It’s part of the package. When there is a cardiovascular signal, we don’t think you can adequately provide labelling in a big enough black box that defines the patients at risk to the degree of confidence that will make the FDA comfortable with any of these drugs. We think this is a close call between asking the company to produce a REMS program that provides this extra help for the prescribing physician or withdrawing the drug, i.e, limited distribution or no distribution.
September 14, 2010 is the PDUFA Date that’s been set for Savient’s KRYSTEXXA (pegloticase) which has been submitted for the treatment of gout. The BLA was resubmitted earlier this year after receiving a Complete Response Letter last summer which highlighted a number of manufacturing deficiencies. The company met with the FDA and agreed on a way forward that resulted in the resubmission which addressed the manufacturing issues but also included a safety update from their clinical trial data base. The company recently announced that it had submitted the final stability update on July 28, 2010.
It all looks good on paper. There’s lots of articles out there providing the safety and efficacy data from a lot of the clinical trials. The company has met with the FDA and provided a resubmission of the requested manufacturing information. So, why doesn’t it feel good to us? We don’t really know for sure but with all of the problems that we’ve seen with recalls for manufacturing related issues and the growing list of products that are in short supply because of these problems, it just follows that the FDA chemistry reviewers and the inspectors just might be spending their time elsewhere. It is a close call but we wouldn’t be surprised to see a 3 month delay on this PDUFA Date to allow the FDA some breathing room.
By September 11, 2010, the FDA must decide on the approvability of ACTHAR (corticotropin gel) for the treatment of certain types of infantile spasms. Following a very positive May 11, 2010 Advisory Committee recommendation, the FDA imposed a 3 month delay on the original PDUFA Date of June 11, 2010 to allow them to work on labeling issues and refine a REMS program for the drug with the sponsor, Questcor. It seems reasonable to believe that the FDA action will be positive, considering the experience the company has with this drug.
The FDA Anti-Infective Advisory Committee will meet on Sept 7, 2010 to discuss the NDA for ceftaroline. The FDA released it’s briefing document and questions before the long Labor Day weekend, perhaps to give the sponsor the opportunity to relax a little before the Tuesday meeting. Relax they should because the FDA reviewers appear to have few if any issues regarding the safety or efficacy of the drug. The questions to the Advisory Committee members from the FDA could not be more basic. We think this one should get a positive nod from the committee.