FDA and Acomplia: Stuck on Each Other?

March 7, 2007

Pharmaceutical Executive

Volume 0, Issue 0

Third regulatory delay highlights difficulty of developing weight loss products.

A throng of plus-size Americans chanting "Free Acomplia now!" and "How many more have to diet?" descended on FDA's Rockville, MD-based headquarters this week, blocking doors and smashing windows to protest the agency's third delay of approval for the much-hyped anti-obesity drug.

We're joshing, of course--demand for Sanofi-Aventis's fat fighter, which is already marketed in 12 countries with full-year sales of over $40 million, hasn't yet reached quite that pitch. But with its next up-at-bat postponed until late July, the ever-growing costs and complications facing the French drug giant may help explain why other companies are leery about entering a market with such lucrative potential.

The Paris-based firm's silence has only deepened the mystery over the reasons for the FDA delay. In a sparsely worded statement, executives noted they had submitted more documents to FDA but named only their Serenade study--which shows that the drug doesn't only cause weight loss but improves cholesterol, blood pressure, and blood sugar. Still, reports of adverse psychiatric adverse events like depression and anxiety have dogged Acomplia (rimonabant), a cannabinoid type 1 receptor blocker that targets brain centers.

Public health officials and payers have long been warning our fast-food nation that "an epidemic of obesity" will add up to spiraling healthcare costs for related conditions--a predicament that may well make reimbursement for weight-loss drugs look like a thrifty alternative. Nevertheless, only two drugs have been approved to treat it: Abbott's Meridia (sibutramine), an appetite suppressant, and Roche's Xenical (orlistat), a drug that blocks fat absorption and is now sold over-the-counter by GlaxoSmithKline as Alli.

"With the health consequences of no therapy, we are shocked at the limited number of companies with late-stage therapies," concluded a report from Susquehanna Financial Group on specialty pharmas. "The surgery options lead to impressive weight-loss results--however, it should be viewed as a treatment of last resort."

But Allan Haberman, principal of consulting firm Haberman Associates, noted that there are ongoing difficulties with developing anti-obesity drugs. While the prescription for weight loss is simple--eat less, exercise more--replicating the results biologically is far from it.

Multiple factors go into appetite and eating, from the psychological to various signaling processes that occur between the brain, liver, muscles, endocrine system, pancreas, and so on. And since obesity has a social construction as well as a physiological one, collecting data from animal studies is difficult. "The standard models in mice are very extreme," Haberman said. "They're like nothing in humans." He added that the answer may come in the form of a pill that hits multiple targets, and even that might still need to be combined with behavior modification.

Yet the regulatory and scientific hurdles haven't entirely blunted the hunger for a silver bullet. Heavy-hitters AstraZeneca, Merck, and GlaxoSmithKline are among the companies vying for a slice of the, er, pie.