FDA Panel Vote Against Vivus Brings More Obesity Drug Questions

16th Jul 2010 18:38

By Thomas Gryta Of DOW JONES NEWSWIRES NEW YORK (Dow Jones)--A Food and Drug Administration panel review of Vivus Inc.'s (VVUS) experimental weight-loss drug Qnexa was expected to bring clarity to the approvability of the latest crop of obesity drugs, but instead it only has raised more questions. The rejection, by a vote of 10 to 6, by the panel of outside experts was largely driven by the lack of long-term safety data on a drug that could be used by millions of Americans for an indefinite period. That panel's concerns, especially about the lack of long-term data, seemed to differ from FDA's assessment of the drug, as represented in briefing documents before the meeting. It is unclear if the panel's worries are specific to Qnexa or if they represent a general nervousness about obesity drugs in general. The obesity drugs under review by the agency, including Arena Pharmaceuticals Inc.'s (ARNA) lorcaserin and Orexigen Therapeutics Inc.'s (OREX) Contrave, all work by affecting the patient's central nervous system to quell appetite. Although the need is high, the area has been plagued with multiple disappointments, tough regulators and lackluster sales. No new treatments have been approved since 1999 in the U.S. If the panel's issues were about Qnexa, then the other drugs, and even Vivus, may have a shot at swaying the FDA with data and post-marketing plans to mitigate any risks. But if the concerns are about obesity treatments in general, which could be taken for a long time by many patients that have no other major health issues, then all the drugs may have major hurdles. Vivus will work with the FDA and remains confident in the approvability of Qnexa, which will have two-year data by the end of September, but the path is unclear without feedback from the FDA itself. Qnexa is a combination of the stimulant phentermine, which cuts appetite, and topiramate, which increases the sense of feeling full. Both drugs have been on the market for years. Notably, Vivus' studies of the drug were done under a special protocol assessment, an agreement with the FDA on study design that meets regulatory requirements for a new drug application. The FDA's briefing documents said "both drugs have reasonably well-established safety profiles because of their widespread use." Overall, the briefing documents were widely viewed as benign, raising known questions about safety, including neurologic and psychiatric effects, cardiovascular impact, and the potential for the drug to cause birth defects. The agency said in the documents that the side effects "were not unexpected based on the known safety profiles of phentermine and topiramate." Given the tone of the documents and even the discussion of the panel, the vote surprised many observers, including FDA officials who spoke to the media afterward. After listening to the entire panel discussions, John Fraunces, managing partner at Synaptic Capital Group, believes the panel wants to approve new obesity drugs. But the totality of the side effects paired with the need for longer data were too great for the voters to overcome, he said. Fraunces owns shares of Orexigen and Arena. Although the FDA is free to approve the drug, it is rare for it to go against a panel recommendation. Needham & Co. analyst Alan Carr said it would be a challenge for the agency to approve Qnexa without committee support, especially with the recent focus on safety. Safety was in the spotlight this week as the same panel reviewed GlaxoSmithKline PLC's (GSK, GSK.LN) diabetes drug Avandia to determine if it should be pulled from the market. Many have speculated that the Avandia review made the Vivus panel concentrate on side effects rather than Qnexa's effectiveness in weight loss. Canaccord Adams analyst Adam Cutler believes the panel had Qnexa-specific concerns and worries that the drug would be used by a wider population beyond any label restrictions. That is certainly an issue that could impact Arena and Orexigen as they face their own reviews, although Cutler believes that those companies may have a better chance at passing the panel's scrutiny. Lorcaserin has a relatively clean safety profile, and Arena's clinical trials were closely monitored for heart problems because the drug's mechanism is similar to fenfluramine, which was pulled from the market in 1997 as part of the notorious fen-phen combination. One of its large two-year studies was published in the New England Journal of Medicine this week. Meanwhile Orexigen's Contrave will face the FDA panel review last, in December, and that time may allow it to better prepare for the meeting. The drug is viewed as having fewer side effects issues, but is also a combination drug that can draw on the long-term data of its components. Regardless of the positives of these drugs, they have numerous issues and FDA panels are notoriously unpredictable. Furthermore, many observers believed that Qnexa had a strong and thorough case for approval right up until Thursday's vote. -By Thomas Gryta, Dow Jones Newswires; 212-416-2169; [email protected] (END) Dow Jones Newswires July 16, 2010 13:38 ET (17:38 GMT)