Sanofi-Aventis Weight-Loss Drug

The Food and Drug Administration Monday said Acomplia, a proposed weight-loss drug by Sanofi-Aventis SA, was effective at promoting weight loss but increased the rate of suicidal thoughts and behaviors.

Acomplia is sold in several European countries and Sanofi-Aventis, Paris, is seeking approval to sell the drug in the U.S.

Acomplia, which would be sold under the brand name Zimulti in the U.S., faces a review Wednesday by an FDA panel of outside medical experts. The FDA typically follows its panels' advice, but isn't required to do so. The FDA is set to make a final decision on whether to approve the drug by the end of July.

In briefing documents posted to its Web site Monday, the FDA said the 20-milligram dose of Acomplia was "associated with statistically and clinically significant weight loss." However, the FDA said it was concerned about an increase in psychiatric side effects as well as seizures. Sanofi had studied a 5- and a 20-milligram dose. The FDA said the 5-milligram dose wasn't effective at helping people lose weight.

Sanofi is seeking FDA approval to sell a 20-milligram dose to people considered obese and to people who are overweight who have at least one cardiovascular disease risk factor such as high blood pressure. Studies of the drug typically showed patients on the drug lost about 15 pounds over the course of a year while those in the placebo group lost about three pounds. They also had gains in HDL, or "good," cholesterol and declines in decline in triglyceride levels, or a type of fat found in the blood.

Acomplia is designed to help block a chemical in the endocannabinoid system, a physiological system in the body that is believed to play a role in how the body regulates food intake. The FDA is concerned, however, that blocking the same chemical could increase the risk for other problems including mood disorders and neurodegenerative disorders like multiple sclerosis.

The FDA reviewed clinical studies of the drug as well as post-marketing reports of the drug from Europe. The agency said the 20-milligram dose of Acomplia "statistically, significantly increased suicidality" compared to placebo or a fake drug. Suicidality is a term used to describe an increase in suicidal thoughts and behaviors and doesn't refer to completed suicides.

The agency also said there was a higher rate of other psychiatric side effects among Acomplia users and the drug increased the risk of seizures. The agency said one set of studies showed 26% of patients on the 20-milligram dose of Acomplia reported a psychiatric side effect -- ranging from depression to insomnia -- compared to 14% of patients in the placebo group.

In its briefing document, Sanofi said the "overall benefits in body weight, waist circumference and metabolic parameters...outweigh the risks that are manageable in clinical practice." The company said it would recommend that Acomplia not be used in patients with an existing psychiatric disorder like major depression and that the drug be used "cautiously" in patients with epilepsy, which causes seizures.

Last February, the FDA rejected Acomplia as a smoking-cessation product and said it needed more information on psychiatric side effects before it would consider approving the drug as a weight-loss treatment.

Courtesy of The Wall Street Journal

Steve - this concurs with what we said in our April issue of Bonnie's Special Report.

The psychiatric side effects that accompany this drug may have been the "unknown" factor causing a 50% dropout rate in short-term trials. Of those left in the trials, there were still a statistically significant number of subjects who experienced severe mental side effects.

Given the fact that the drug does affect the neurological system, we should not be surprised by this.

We are anxiously awaiting the recommendations from Wednesday's panel. Billions are riding on this drug.