Two New Weight Loss Drugs Approved by FDA Advisory Committee

Government advisers recommended approval last week of a weight-loss drug developed by Arena Pharmaceuticals, making it likely that a new obesity treatment will reach the market this year. This makes two new diet pills that could hit the obesity market this year. The possible approval of lorcaserin, developed by Arena Pharmaceuticals is expected on July 17^th while a decision on Qnexa (phentermine/topiramate), developed by Vivus and endorsed by the same committee, is also expected by the same day.

An advisory committee to the Food and Drug Administration voted 18 to 4, with one abstention, that the benefits of the drug, lorcaserin, outweighed the risks. If the FDA approves the drug by its scheduled deadline of June 27, lorcaserin would be the first new prescription diet pill to reach the market in 13 years. The agency does not have to follow committee recommendations, although it usually does.

Lorcaserin (APD-356, trade name Lorqess) is a weight-loss drug developed by Arena Pharmaceuticals. It has serotonergic properties and acts as an anorectic.

Another obesity medicine, Qnexa, developed by Vivus, was endorsed by the same committee in February. The FDA is scheduled to decide whether to approve it by July 17. Lorcaserin and Qnexa (phentermine/topiramate) received negative votes from the committee in 2010, and the FDA then did not approve them. More on Qnexa

The positive votes this time stem in part from new data provided by the companies. But they also seem to reflect a growing feeling, voiced by several members of the advisory committee, that new tools are needed to treat a major health problem.

Still, many of those who voted for approval at the meeting, expressed only muted enthusiasm for lorcaserin, saying it did not help people lose much weight. "It is not really the answer to the obesity problem, but it may be a steppingstone to help us out," said Dr. Eric I. Felner, a pediatric endocrinologist at Emory University who voted in favor of approval.

Two main safety concerns led the FDA to turn down lorcaserin in 2010. One was that the drug appeared to cause tumors in rats. Arena presented new data that seemed to persuade some, but not all, committee members that the rat experience would not apply to people, especially at the doses to be used. The other concern, which appeared more worrisome to the committee, was whether lorcaserin damages heart valves. Lorcaserin works the same way as two drugs that were associated with the fen-phen diet pill combination but were withdrawn from the market in 1997 because they damaged heart valves.

Arena presented data showing that its drug binds strongly to the receptor on cell surfaces that helps control appetite but only weakly to a similar receptor implicated in the valve damage. Results of the clinical trials did not show a statistically significant increased risk of valve damage for patients getting lorcaserin, but also did not rule out such a risk to the extent desired by the FDA.

"I think a signal remains," said Dr. William R. Hiatt, a cardiologist at the University of Colorado, referring to valve damage. Still, he voted in favor of approval, saying patients could be monitored for signs of valve damage.

While the risks of the drug did not seem huge to the committee, neither did the benefits. In two big clinical trials, patients who took lorcaserin lost an average of 5.8 percent of their body weight after a year, compared with 2.5 percent for those getting a placebo. The difference between the two groups, 3.3 percentage points, fell below the FDA's standard for approval, which is five percentage points. However, 47 percent of those on the drug lost at least 5 percent of their weight after a year, double the 23 percent of those in the placebo group, satisfying a different criterion for approval.

Those who argued in favor of the approval said that lorcaserin would help some people lose significant amounts of weight, while patients not losing weight would stop taking the drug and not be exposed to side effects.

According to a study presented at the European Congress on Obesity, held from May 9 to 11 in Lyon, France, A new combination treatment of controlled-release phentermine/topiramate (Qnexa) (PHEN/TPM CR) leads to significantly greater weight loss than a placebo even in individuals with significant obesity-related comorbidities.

In the latest Qnexa study, Stephan Rössner, M.D., Ph.D., from the Karolinska Institutet in Stockholm, and colleagues randomly assigned 2,487 subjects to placebo or one of two doses of PHEN/TPM CR: 7.5 mg/46 mg (7.5/46) or 15 mg/92 mg (15/92) for 56 weeks. Subjects were categorized according to the Edmonton Obesity Staging System (EOSS), which measures obesity-related morbidity, with most subjects having weight-related chronic disease (2,170 individuals) or established end-organ damage (180 individuals). The researchers found that PHEN/TPM treatment was associated with significantly greater weight loss compared with placebo across all EOSS categories. Weight loss increased in a dose-response manner and ranged from 1.5 to 2.3 percent for placebo, 6.8 to 8.6 percent for 7.5/46 PHEN/TPM, and 9.5 to 10.5 percent for 15/92 PHEN/TPM. Dry mouth, constipation, and paraesthesia were the most common adverse events.

"In this study, subjects with established comorbidities treated with PHEN/TPM CR showed significantly greater weight loss than placebo regardless of baseline EOSS," Rossner and colleagues conclude.

FDA Briefing Document