FDA Reviewers Explain Agency's New Obesity Drug Paradigm in NEJM

Six drug reviewers with the US Food and Drug Administration (FDA) have written an explanation of the safety and efficacy paradigm used to assess new anti-obesity therapies and approve two new obesity drugs-the most approved in one year since a number of high-profile safety concerns resulted in many of the drugs being withdrawn from the market.

The graveyard of such therapies is well populated. Aminorex, a stimulant, was withdrawn in 1972 after it was shown to cause pulmonary hypertension. Dexfenluramine, an appetite suppressant, damaged some patients' heart valves. Phenylpropanolamine, a stimulant and appetite suppressant, was associated with strokes in younger women. Rimonabant, an appetite suppressant, increased thoughts of suicide in patients. And sibutramine, an appetite suppressant, caused heart attacks in patients.

All were subsequently withdrawn from the market, but not before casting a pall over the entire therapeutic class.

But things are changing at FDA, the reviewers say in an article in the New England Journal of Medicine (NEJM), with regulators approving two new drugs in 2012 under a newly conceived paradigm aimed at reducing cardiovascular and other safety risks for patients who would stand to benefit from such drugs less than obese patients.

"Because these drugs are associated with potentially serious risks and are intended to be taken long-term, it is important that their use be limited to patients for whom they are indicated," the reviewers said.

Both Arena Pharmaceutical's Belviq (lorcaserin) and Vivus' Qsymia (hydroxytryptamine) were approved with a label requiring they be marketed only to those with a body mass index equal to or greater than 30, or equal to or greater than 27 with at least one weight-related health complication.

In addition, as a condition of approval, Vivus and Arena will be required to conduct postmarketing studies following the outcomes and adverse events of patients taking the drugs. "The FDA acknowledges that there is more to learn about these drugs," the reviewers wrote.

The drugs will also be combined with treatment escape criteria, with FDA recommending that any patient not losing at least 3-5% of baseline body weight after 12 weeks immediately cease treatment.