FDA to review rejected weight loss drug Qnexa

By Dr. Ananya Mandal, MDFeb 21 2012

The weight loss pill Qnexa has been once rejected by the FDA over safety concerns. But this Wednesday it will get a second chance before an FDA advisory committee. Qnexa maker Vivus Inc. hopes something might come out of this second chance. The company will be submitting new safety data from patients who took Qnexa for a second year after completing a one-year clinical trial.

Qnexa combines two currently approved drugs. One is the appetite suppressant phentermine, the safer "phen" part of the infamously unsafe fen-phen diet drug. The other half of Qnexa is the seizure/migraine drug topiramate. The topiramate label lists some side effects: eye problems, decreased sweating and increased body temperature, acidic body fluids, suicidal thoughts and behaviors, and fetal toxicity.

Over the past two years, the FDA has rejected pills from three drug companies, Arena Pharmaceuticals Inc., Orexigen Therapeutics Inc. and Vivus.  All three companies are competing to have their weight-loss drug hit the market first because there has not been a new weight-loss drug in over a decade.  All three companies are currently preparing their products for resubmission for FDA approval.

Obesity is a serious problem in the U.S., meaning weight-loss drugs have an untapped population.  There is a significant need for new weight-loss drugs to help people fill the gap between diet and exercise.  There are other methods to lose weight, besides diet and exercise.  Bariatric surgery has been shown to help, but the procedure is involved and invasive. The FDA is cautious about approving weight-loss drugs because two-thirds of Americans are overweight, representing millions of Americans who may take these weight-loss drugs.  So the FDA wants to be sure that whichever weight-loss drug is approved is safe for the population.

FDA’s main concerns are heart risk and birth defects and these were not big issues in the new safety trials. Neither were worries about increased suicide risk, mental dulling, or too much acid in body fluids. There was however evidence of increased heart rate and acidic body fluids in people taking Qnexa. The FDA states that “only a long-term” study can tell whether Qnexa increases the risk of heart disease in obese people already at high heart risk. One question before the panel is whether Vivus must conduct such a study.

A disturbing number of women in the clinical trials got pregnant, even though they had agreed to be on birth control and had regular pregnancy checks. One of the ingredients in Qnexa is linked to birth defects, although none were seen in the clinical trial. Since 36% of U.S. women are obese, the FDA worries that a lot of pregnant women will be exposed to Qnexa.

On average, people taking the dose of Qnexa proposed for approval lost 6.6% of their body weight. For approval, the FDA requires that a drug result in average loss of at least 5% of body weight. In one study, 62% of obese and overweight people taking Qnexa lost at least 5% of their body weight - about three times as many as in the placebo group. The FDA standard is that 35% of people must lose 5% of body weight. In a follow-up study, people continuing to take Qnexa for a second year regained some of the weight they lost the first year. They did not regain as much weight as people taking a placebo.

The last panel voted 10 to 6 against approval. But a lot of those voting said it was a close call. This year, there are 22 panel members scheduled to vote. Twelve of them were on the last panel. Last time, seven of them voted "no" to approval, and five voted "yes."

Currently there is just one prescription drug on the market for long-term weight loss: Roche's Xenical, which is not widely used because of modest weight loss results.