News came across this afternoon (Feb 17) that Sanofi received an approvable letter on rimonabant for weight management and an actual non-approvable letter for smoking cessation. There were no details given on what further data Sanofi needs to provide to the agency, on further trials that may need to be done, etc.
While we believe there is no question that rimonabant has provided metabolic benefit for some who took it, the questions about safety loom larger - the approvable letter for weight management certainly seems to relate to lack of confidence by the FDA on this front. A study came out earlier this week in JAMA, the psychiatric concerns about which we detailed on our Feb 15 blog entry (www.closeconcerns.com). The adverse event table for RIO-North America is on page 772 of the JAMA piece and shows the adverse events detail, the most concerning of which are the psychiatric adverse events as we noted a few days ago. We can't imagine, for example, that footnote about a gunshot doesn't refer to a suicide and a 2.7x higher drop out rate for psychiatric events should certainly raise eyebrows - plus a 50% dropout overall - where are all these people?! While no direct conclusions can be made, the data certainly suggested more study should be required, and we are very glad to see that the drug didn't receive outright approval.
We expect more data has been requested in the approvable letter; following this, the FDA could undoubtedly benefit from a panel, in which obesity experts, cardiologists, endocrinologists, and psychiatrists could weigh in. This is despite the extent to which some say the advisory panel process is broken - we don't entirely disagree, but just advocate fixing it! Ultimately, the actions today suggest that the ultimate drug approval may be years away. This is further suggested by the fact that on the smoking cessation front, the company received an actual non-approvable letter - seems likely that there were major addiction worries and concerns about off-label use, etc., though of course this is speculative.
Sanofi confidence HAS been projected within the financial community throughout the development of the drug, and especially within recent months, which had been surprising. For example, in late January, the company characterized the collaboration with the FDA as excellent, noted that they have developed the product with close coordination with the authorities, and said that they "remain confident that we will launch Acomplia in the second quarter of 2006" - this comment seemed especially surprising in front of an agency decision. Notably, Sanofi management had said in mid May 2005 that it would position this drug as prevention for metabolic disorders - seemed a little of the cart getting ahead of the horse, since they hadn't even been willing at that point to disclose what indications for which they were filing (turns out to be obesity management and smoking cessation). Primary endpoints for all RIO trials relate to weight management while secondary endpoints cover lipids, waist circumference, and blood pressure, elements of most metabolic syndrome definitions.
One more speculative suggestion - this action may also signal that a non-request for a panel by the FDA should perhaps be viewed more ominously when there are safety questions - although Amylin's Byetta also didn't receive a request for a panel, its clean safety profile certainly seems a major advantage of the drug.
From a patient perspective, it is a great signal to see that the FDA is taking safety very seriously across all fronts (cardiovascular, CNS, etc.), especially among areas that are more "gray" and less tangible. We believe today's news also implies that we are still very far away from a metabolic syndrome indication for any drug.
What next? Sanofi has analyst meetings Feb 24 in Paris and March 22 in New York, where more information on next steps with the FDA may be given - it would have seemed that the analyst meeting in Feb was scheduled to coincide with news about approval. It will be interesting to see what is happening on the European approval front - Sanofi acknowledged in an analyst Q&A that they had also filed rimonabant in Europe.