Summary
The recent FDA release of preliminary data from the first large-scale, randomized, cardiovascular outcome trial ever conducted for the treatment of obesity comes as a shock. While full data are not available (and the level statistical significance was not given), the fact that cardiovascular events increased rather than decreased with an obesity treatment that is at least moderately effective in reducing weight is an unwelcome surprise. Major changes in FDA review of new obesity drugs may occur.
Analysis
The FDA issued a warning on 11/20/09 that preliminary results from the SCOUT study show increased risk of cardiovascular events in obese high risk patients treated with Meridia (14% higher event rate). This result is surprising, and may lead the FDA to tighten restrictions on approval of new obesity drugs:
1. It seems likely that the FDA will request a cardiovascular safety review for new obesity approvals (similar to that now required for diabetes drugs). Given the relatively healthy young patients enrolled in obesity studies, this might require additional 12-18 month studies in higher risk patients in order to accrue the requisite number of events.
2. It is also possible that the FDA will use the SCOUT results to demand a higher level of safety for obesity drugs than for diabetes drugs, namely an adequately powered, long term outcomes study prior to approval. The rationale for this would be the history of increased events in the SCOUT study and the safety issues raised by the phen/Fen debacle.
3. Any obesity drug that increases BP (as Meridia does) will likely to be examined much more rigorously (this includes phentermine).
These surprising data have implications for the development programs and approval of Qnexa (Vivus), Contrave (Orexigen), Empatic (Orexigen), lorcaserin (Arena), pramlintide/davalintide/metreleptin (amylin), and GLP-1 analogs (Amylin, Novo Nordisk, Roche) for obesity indications.
