Once again affirming ongoing safety concerns about the anticipated widespread use of diet pills, the FDA issued a so-called Complete Response Letter for Contrave, a drug developed by Orexigen Therapeutics. The move comes less than two months after an FDA advisory panel recommended the pill for approval, but also voted in favor of requiring additional studies to gauge cardiovascular risks (back story).

In disclosing the rejection, Orexigen ceo Michael Narachi disclosed the agency wants the drugmaker to conduct a randomized, double-blind, placebo-controlled trial. “We are surprised and extremely disappointed,” he says in a statement. Had the FDA approved Contrave, the pill would become the first new prescription diet drug to reach US consumers since 1999, when the FDA endorsed Roche’s Xenical. Contrave, by the way, combines the Wellbutrin antidepressant and a sustained release form of naltrexone, an opioid blocker used to treat addictions to alcohol and painkillers.

“The unwelcome ’surprise’ is the requirement for a pre-approval CV outcomes study,” writes Leerink Swann analyst Josh Schimmer. “Recall that, at the FDA advisory panel meeting in December, the panel voted 11-8 that a CV trial should be required AFTER approval. Unless Orexigen can convince the FDA that the trial can wait until post-approval, the company faces a cloudy future, particularly since Takeda does not assist in pre-approval CV study costs.” Takeda Pharmaceuticals has a marketing deal with Orexigen (see here).

The FDA rejection marks the third consecutive time in recent months that a new diet drug has been rejected over some type of side effect issue, which is not surprising, given that each pill demonstrated reason for concern. The others are Lorqess from Arena Pharmaeuticals (see here) and Qnexa from Vivus.

As we have noted previously, the agency is not only much more safety conscious in general, but its actions indicate a heightened awareness that diet drugs pose an outsized risk since so many people can be expected to use them, appropriately or not. After all, this is an era when the FDA is under pressure to ensure that safety is a high priority. And this is hardly surprising in light of several controversies over manipulated clinical trial data and side effect disclosures involved various meds. Diet pills, however, have merited special attention thanks to the 1997 withdrawal of part of the fen-phen cocktail, which was sold by Pfizer’s Wyeth, over heart and lung damage.

The FDA may recognize a need for drugs that help people lose weight, but at what cost? How much safety risk can be tolerated when drugs offer little to modest weight loss? Such scrutiny led Sanofi-Aventis three years ago to give up on winning FDA approval for Acomplia due to psychiatric side effects (see this). And recently, Abbott Laboratories reluctantly withdrew its Meridia pill under pressure from the agency.

Meanwhile, the overweight will have to exercise a little more and investors, well, they will have to exercise better judgment.

pic thx to alan cleaver on flickr