FDA advisory panel votes in favor of approving obesity drug Qnexa

By Deborah Kotz, Globe Staff

SILVER SPRING, Md. -- A US Food and Drug Administration advisory committee voted overwhelmingly this afternoon in favor of approving the anti-obesity drug Qnexa. It would be the first new prescription weight-loss drug in 13 years -- and only the second one on the market -- if the agency follows the panel’s recommendation, which it usually, but not always, does. The committee voted 20 to 2 to approve the drug.

Qnexa -- a combination of the appetite suppressant phentermine and the seizure and migraine drug topiramate -- was turned down by the FDA in 2010 because of safety concerns over heart risks and birth defects in women who become pregnant while taking the drug.

After considering study data from following patients for two years, the expert panel determined that the weight-loss benefits outweighed the risks of two potential side effects: an uptick in cleft palates in children born to women who took topiramate while pregnant, and a modest increase in heart rate that could lead to heart troubles down the road. The 2010 decision was based on just one year of data.

“I think this is the most efficacious drug we’ve seen,” said Dr. Lamont Weide, chief of diabetes and endocrinology at the University of Missouri who voted to approve the drug.

In clinical trial data submitted to the FDA by manufacturer Vivus, patients who took higher and lower dose versions of the drug for two years lost between 3 to 10 percent of their weight on average, compared with a 2 percent loss in those who took placebos. The amount of weight lost by patients taking Qnexa led to an improvement in obesity-related health conditions, such as a reduction in high blood pressure and the diabetes marker hemoglobin A1C, and a boost in “good” HDL cholesterol levels.

But those on low-dose and high-dose versions of Qnexa, as well as the placebo group, began to regain lost weight after the first year of the study, so it’s not known how long the effects of the drug will last for those who take it for several years.

While too few pregnancies occurred during the clinical trial to measure an increase in birth defects, a recent study on topiramate in women who took the drug during pregnancy to control seizures found that cleft lip and palate occurred in 0.29% compared to 0.16% in women with prior exposure to the drug. Other studies suggest an even higher risk, which means that young women prescribed Qnexa for obesity would have to be careful about using birth control while on the drug. (Those involved in the clinical trial were told to use two methods of birth control.)

Vivus also reported a slight increase in resting pulse -- a few beats per minute -- in Qnexa users which expert panel members said could be a signal for an increased risk of heart problems. The trials weren’t large enough or long enough to measure cardiac events like heart attacks.

Prescription weight-loss drugs have been marked by far more failures than successes. Twenty years ago, the combination of phentermine and fenfluramine was taken by millions until it was found to cause life-threatening heart valve problems. While Orlistat remains on the market, Meridia (sibutramine) was withdrawn less than two years ago after it was linked to an increased risk of heart attacks and strokes.

Two experimental drugs -- Lorqess and Contrave -- were recently rejected by the FDA because of unanswered questions about safety concerns and relatively modest weight-loss benefits. Contrave (a combination of naltrexone and bupropion) had been given the thumbs up by an FDA advisory committee before being rejected by the agency itself. Both may win approval in the future if further clinical studies satisfy the FDA.

Advisory committee member Dr. Allison Goldfine, assistant director of clinical research at Joslin Diabetes Center in Boston, said she voted in favor of Qnexa because she sees the drug as filling a much needed gap between bariatric surgery -- which has its own set of risks -- and diet counseling. But she added that she was still concerned about unknown safety risks and, like other panel members, she called for a post-approval follow-up study to be conducted by the manufacturer.

Others, though, pressed for these studies to occur before Qnexa’s approval. “I’m concerned that a decision to approve the drug at this stage would be a mistake,” said Dr. Michael Lauer, director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute, who voted against approval. “There’s a real possibibilty that this agent may help people lose weight, yet it [may] wind up causing heart attacks, strokes, and a higher death rate.”

Before the vote, members of the public, including obesity research advocates, spoke in favor of Qnexa’s approval, questioning why the FDA appears to be dragging its feet in recommending new obesity drugs when it doesn’t have the same hesitation for, say, diabetes or heart drugs. “Obesity is not a condition of personal choice,” said Chris Gallagher of the American Society for Metabolic and Bariatric Surgery. “It should be subject to and evaluated by the same criteria as drugs used for other chronic diseases.”

Thomas Hughes, president of Cambridge-based pharmaceutical company Zafgen -- a start-up developing its own obesity drug -- expressed his support for the committee vote. “We see the committee’s recommendation as a very positive signal; new and effective agents for the treatment of obesity, with acceptable risk/benefit profiles are both needed and are of value.”

Deborah Kotz can be reached at dkotz@globe.com. Follow her on Twitter @debkotz2.