By JENNIFER CORBETT DOOREN
WASHINGTON -- The Food and Drug Administration Monday said Acomplia, a proposed weight-loss drug by Sanofi-Aventis SA, was effective at promoting weight loss but appeared to double the rate of suicidal thoughts and behavior.
Acomplia is sold in several European countries and the Paris company is seeking approval to sell the drug in the U.S., a key market that would likely propel it to blockbuster status of $1 billion or more in annual sales. 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. Acomplia is also known by its generic name, rimonabant.
WSJ's health blogger Jacob Goldstein discusses new FDA documents that state Acomplia from Sanofi-Aventis was effective at promoting weight loss but appeared to double the rate of suicidal thoughts and behavior.
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. The panel will be asked to decide several questions, including whether rimonabant should be approved or if additional studies are needed. The panel will also have to decide if it believes rimonabant increases the incidence of "suicidality," psychiatric and neurological adverse events, or side effects and seizures.
Suicidality is a term used to describe an increase in suicidal thoughts and behaviors and doesn't refer to completed suicides.
In briefing documents posted to its Web site Monday, the FDA said the 20-milligram dose of rimonabant 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.
Rimonabant 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 rimonabant is "statistically, significantly increased suicidality" compared to placebo or a fake drug.
The agency said a detailed meta-analysis of the suicidality data will be presented to the advisory panel Wednesday, but noted that patients on rimonabant were twice as likely to report an increase in "suicidality."
The FDA also said there was a higher rate of other psychiatric side effects among rimonabant 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 rimonabant reported a psychiatric side effect -- ranging from depression to insomnia -- compared to 14% of patients in the placebo group.
"We anticipate that much of the discussion at the advisory committee meeting will center on the relationship between rimonabant and depression, and on the methodology, results and interpretation of FDA's meta-analytic assessment of suicidality from completed rimonabant studies," the FDA said in a letter to panel members.
In its briefing document, Sanofi said that 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 rimonabant 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.
Sanofi shares edged lower on the New York Stock Exchange, falling 36 cents, or 0.8%, to $45.14.
Write to Jennifer Corbett Dooren at jennifer.corbett-dooren@dowjones.com
