Qnexa, a Promising Weight Loss Drug, Fails to Gain Regulatory Approval

Earlier this week, the FDA chose not to approve the weight-loss drug Qnexa. Qnexa is a combination of two currently approved drugs: phentermine, which is approved for short-term weight reduction, and topiramate, which is approved for the treatment of epilepsy and migraines. When combined, these two drugs have shown considerable promise as a treatment for long-term weight loss. Over two years, obese patients engaging in a diet and exercise regimen who were treated with Qnexa achieved 11.4% weight loss with the full dose and 10.4% with the medium dose compared to just 2.4% on placebo (in ert pills). Furthermore, Qnexa has been found to significantly reduce blood pressure, lipid (cholesterol) levels, and, in other trials for individuals with type 2 diabetes, A1c (for more details, please see NewNowNext in diaTribe issue #21). The most commonly reported side effects reported were dry mouth, constipation, altered taste, and insomnia. Although promising, the members of the FDA Advisory Committee that convened this past July to review Qnexa advised the FDA not to approve the drug over concerns with possible long-term safety issues including cardiovascular risk (due to slightly increased heart rate with Qnexa), teratogenicity (the risk for birth defects), and psychiatric problems (see NewNowNext from diaTribe issue #25 for more details). The FDA chose to follow the advice of the Advisory Committee and decided not to approve the drug. Instead, the agency has asked Vivus, the maker of the drug, to: 1) provide proof that the increased heart rate observed with the drug does not increase long-term risks for cardiovascular events (such as heart attacks and strokes); 2) provide a more complete assessment of the teratogenicity risk in pregnant women and a plan to evaluate and mitigate this risk in women; and 3) provide the complete results from the two-year phase 3 study that the company recently completed. Vivus appears confident that Qnexa will eventually gain approval and plans to submit all of the requested material within six weeks. Following submission, the FDA will take between two to six months to review the material, placing the next possible approval date within the first half of 2011.

Since the withdrawal of Meridia (sibutramine) from the market earlier in October, Xenical (orlistat) remains the only weight loss drug approved for long-term use in the United States. Yet, this drug has shown only modest efficacy in reducing weight and is associated with unpleasant side effects such as frequent, oily bowel movements. While we believe that diet and exercise should remain central to treating obesity, more tools are clearly needed to combat the ever-growing obesity epidemic. In our view, effective medications like Qnexa can fill this void and provide help to potentially millions of people who are unable to achieve adequate weight control through diet and exercise alone. We eagerly look forward to hearing the FDA’s next decision on Qnexa early next year. --BK