FDA panel votes against approval for weight loss drug

The FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 10-6 against approval of combination phentermine plus topiramate.

The drug (Qnexa, Vivus) was proposed as an adjunct to diet and exercise for weight management in obese patients with a BMI of 30 or a BMI of 27 with weight-related comorbidities.

“While I agree there is a significant obesity epidemic in the United States … my concerns were the public health consequences, given the long list of safety risks and the strong pent-up market demand,” panel member Elaine H. Morrato, DrPH, MPH, assistant professor in the department of health systems, management and policy at the University of Colorado, Denver, said of her vote. “The drug will be used by millions of patients over long periods of time far exceeding the label indications for use and duration of clinical experience that we have.”

Ed J. Hendricks, MD, medical director at the Center for Weight Management, California, voted yes, and said the data presented on phentermine plus topiramate meet FDA efficacy thresholds and show that the drug is “reasonably safe” in the target population of obese patients.

“While I agree that the population at large needs to be protected from dangerous drugs, one-third of the population is already obese and there is a very large segment of the population who is heading that way,” Hendricks said.

Despite the negative recommendation for approval, a number of panelists said the decision was difficult. Longer follow-up, wider subgroup research and a greater understanding of adverse effects were common concerns listed for denying approval.

Safety was the main topic of discussion at the meeting. Adverse events of particular concern were related to psychiatric and cognitive events, teratogenicity, metabolic acidosis and cardiovascular events.

Mary Roberts, MD, clinical reviewer for the FDA, presented data showing a 1.5 to twofold greater risk for psychiatric adverse events, a fourfold greater risk for cognitive impairment and an increased heart rate in 20% of patients treated with high-dose phentermine plus topiramate.

“In general, the FDA is in agreement with the company in regards to the weight loss effects of the drug,” Eric Coleman, MD, deputy director of the division of metabolism and endocrinology products in the FDA’s Center for Drug Evaluation and Research said at the start of the meeting onset, adding that the decision will be based on safety.

In a statement released by Vivus after the meeting, chief executive officer Leland Wilson said the company is “dissapointed” with the panel’s vote.

“While the final vote was close, and we are encouraged that the committee recognized the efficacy demonstrated in the Qnexa clinical trials, we will work closely with the FDA leading up to our Oct. 28, 2010, Prescription Drug User Fee Act date to address the labeling and safety questions raised during today's proceedings."

While the FDA is not required to follow the recommendations of the advisory committee, it usually does. – by Matthew Brannon

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