FDA sees suicidal behavior with Sanofi drug

By Lisa RichwineMon Jun 11, 5:24 PM ET

People who took a Sanofi-Aventis SA obesity pill in clinical trials were more likely to report suicidal thoughts or actions, U.S. drug reviewers said in an analysis released on Monday.
Food and Drug Administration staff also said a 20-milligram dose of the drug, Zimulti, plus a low-calorie diet reduced weight about 5 percent more than diet alone over one year.
The agency will ask an advisory panel on Wednesday to weigh the possible benefits and risks and decide whether to recommend approval of U.S. sales. Known generically as rimonabant, the drug is sold in 18 other countries under the name Acomplia.
U.S. regulators have delayed a final decision several times amid safety questions.
"We remain concerned about rimonabant's adverse event profile, specifically adverse psychiatric reactions," an FDA staff summary said.
Psychiatric problems "represent the most common and worrisome rimonabant-induced adverse events," the reviewers said. Twenty-six percent of Zimulti patients reported a psychiatric symptom, compared with 14 percent of placebo patients, they said.
Suicidal thoughts were reported for 0.63 percent of Zimulti patients and 0.38 percent of placebo patients, Sanofi said in a separate summary. One Zimulti patient actually committed suicide.
The company said all of the cases were associated with depression or other psychiatric disorders, and it would recommend that the drug not be used by patients with serious, uncontrolled mental illness.
The drug's benefits "clearly outweigh the defined risks that are manageable in clinical practice," Sanofi said. Aside from weight loss, Zimulti reduced waist size and improved levels of cholesterol, blood sugar and blood fats known as triglycerides.
Zimulti works by blocking food craving signals in the brain. Sanofi developed the drug to target brain receptors that trigger intense hunger after marijuana use.
The French drugmaker has predicted in the past that the drug could generate sales of $3 billion a year or more. Sales for the first quarter of 2007 were about $20 million.
Zimulti is an important drug for Sanofi, which faces potential generic competition to key products.
The FDA will ask the outside advisers if they believe Zimulti increases suicidal behavior, other psychiatric problems, neurological problems and seizures, and if the drug should be approved, the staff review said.
The agency usually follows panel recommendations.
Some industry analysts said it was unclear how the panel would decide.
Vontobel analyst Karl Heinz Koch noted that other weight-loss drugs such as Roche AG's Xenical and Abbott Laboratories Inc.'s Meridia are approved even though higher rates of depression are noted on their labels.
"One can throw the dice" on the panel's outcome, Koch said.
The agency is expected to rule on Sanofi's bid for U.S. approval by July 26.
The FDA staff and Sanofi summaries were posted on the agency Web site at
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-fda-backgrounder.pdf.