Sanofi Can Blame Itself for FDA Rejection of Acomplia Weight Drug

Rimonabant/Acomplia by Sanofi-Aventis (SNY) was touted as a blockbuster drug in the obviously lucrative market sector of obesity. Diet and exercise have generally been shown to fail and dieting may actually make obesity more difficult to reverse.

While bariatric (obesity) surgeries are the fastest growing operations in America, they have generally been reserved for the most overweight, the morbidly obese or those likely to die of obesity. Somewhere in the neighborhood of 30% of the U.S. population could qualify for long-term pharmacological treatment.

The recent history of pharmacological treatments has not gone well. The pharmaceutical treatments do cause significant weight loss but side effects have been the rule rather than the exception. First there was Phen-Fen. While effective, cardiologists at Mayo clinic observed and reported that it caused heart valve changes. This report ultimately led to Fen's (fenfluarmine; dexfenfluramine—Wyeth (WYE)) withdrawal from the market and ensuing litigation.

Xenical (Orlistat; Roche (RHHBY)) came next and was touted by the company as a $>1b blockbuster. The company, apparently unhappy with the pace of sales to patients being seen by obesity experts, went directly to the patient with ads. Unfortunately for them, the side effects were branded in the American public's consciousness and prescription rates were disappointing. As a pancreatic lipase inhibitor, it blocks the absorption of dietary fat in the gut. Simply stated, the pizza you ate for lunch goes in the mouth and out of the body as a fatty stool or diarrhea. Gas and stool leakage strategies exist but most patients are immediately disinterested when such a discussion starts with their physician.

If overeating of good or great food is an addiction then addiction-like treatments may be the wave of the future.

Acomplia is a novel treatment that blocks the brain's marijuana or THC receptors. It blocks the MJ munchies and slowly appears to interfere with some of the hedonic or rewarding aspects of eating. Unfortunately, the brain's own marijuana system is extensive and important. All of its functions are not known but it appears important to memory formation, mood, eating, and pain, to name a few obvious candidates. So, it is was not surprising for researchers to discover that a number of patients treated for obesity developed depression out of the blue.

The FDA's open hearings Wednesday on this drug demonstrated a number of things. First, Sanofi-Aventis had done a very poor job in managing the clinical trials of this blockbuster drug. Sanofi did a fine job at promoting the discovery and getting enough market cap to buy Aventis. With the study details, data and the FDA it was a complete bust.

It attempted to use the metabolic effects of the medication in reversing diabetes – like blood markers and risks - and to avoid the psychiatric effects. However, the metabolic experts on the FDA panel were not impressed with the typical weight loss and predicted that millions of patients would be stuck on the medication for years. They feared suicides and depressions without a major weight loss benefit.

Second, Sanofi-Aventis did a very poor job at mobilizing the advocacy community and had few speakers in its corner. Last, when it suggested that it could reduce the psychiatric risks with a plan that it described, it appeared that it was way too little too late. The FDA usually follows the Advisory Panel and no one gave it any reason to do anything but Just Say No.

So, this will become another example of a medication approved in Europe and Mexico, but not America. This drug may have a use in some patients with tobacco or marijuana or other addictions but you have to wonder who is managing this group and potential $1b drug market for Sanofi? This big pharma has lost its way and is lucky to have taken over Aventis scientists, psychiatrists, and pipeline.

The day after the announcement of the unanimously negative vote of the advisory panel for approval of its weight-loss drug Acomplia, Sanofi-Aventis was trading down nearly 8% and downgraded to neutral at both Merrill Lynch and J.P. Morgan.