Diet pill rimonabant (Acomplia / Zimulti) was dealt a major setback on June 13th when an FDA advisory panel of outside experts unanimously recommended that the regulatory agency not approve the novel weight-loss drug for sale in the United States.
The panel voted 14-to-0 that based on data provided to date, it was impossible to conclude that rimonabant has a "favorable risk-benefit profile," and recommended that Zimulti -- as it was to be known in the U.S. -- not be approved to aid weight loss by obese and overweight individuals.
"My level of concern regarding riminobant and psychiatric events is very high," said Dr. Sid Gilman of the University of Michigan. Added Dr. Paul D. Woolf of Crozer-Chester Medical Center: "I am concerned about what we don't know and the dangers we can fall into."
"We had better learn some more before we lunge into massive use," said Dr. Jules Hirsch of Rockefeller University. "I wouldn't in any way suggest that it be approved at the present time for use.
While the FDA is not obligated to follow the recommendations of its advisory panels, it generally does. With a recommendation this overwhelming, the agency almost certainly will decide next month to defer action on Acomplia and await more data -- perhaps keeping it off the U.S. market until a large 50-month trial now underway is completed in 2010.
The drug has been on sale in Europe as Acomplia for almost a year, and is also now available in Argentina, Brazil, Mexico and a handful of other countries.
Members of the FDA's Endocrinologic and Metabolic Drug advisory panel recommended against adding the U.S. to the list of countries where rimonabant is available after unanimously concluding that available safety data is not adequate.
The action came at the end of a day-long hearing during which Sanofi Aventis emphasized clinical trial results showing Acomplia helped many patients to achieve significant weight loss while also producing improvement in a variety of other cardiometabolic risk factors.
While FDA participants generally conceded the weight-loss benefits of rimonabant, they focused their presentations on safety concerns over a novel drug which works by blocking the CB1 receptors in the brain.
"The risks include an approximate doubling in the risk of psychiatric adverse events, an approximate doubling in the risk of sucidiality, an increase in a constellation of neurological events of unkown significance, an increase in nausea and vomiting, and as yet to be identified risks," said the FDA's Dr. Amy Egan. "And there will be further risks."
Sanofi earlier had challenged the FDA's analysis of the data, and insisted that no "causal relationship" has been established between rimonabant and "suicidality."
But the French pharmaceutical company also pledged to immediately begin asking all patients in ongoing clinical trials whether they are having any suicidal thoughts.
"Sanofi-Aventis will be implementing the questionairre discussed today. We will be using it in the clinical trials going forward," Dr. Paul Chew, a Sanofi vice president told the panel. "If you want to get the answer, you have to ask the question."
After the votes, Sanofi issued a statement saying it would "continue to work closely with the FDA to address the committee's recommendations."