FDA Panel Rejects Obesity Drug Zimulti
Experts Concerned About Possible Risks of Suicidal Thoughts in Drug Formerly Called Acomplia
June 13, 2007 -- A new weight loss drug designed for obese adults failed to
win approval from an FDA advisory panel Wednesday, mainly because of fears that
it can lead to depression and suicidal thoughts in some patients.
Outside experts unanimously rejected the bid of Sanofi-Aventis to market
Zimulti (rimonabant) in the U.S. despite its approval in dozens of other
countries. The drug was previously known as Acomplia.
"My level of concern ... is very high," says Sid Gilman, MD, a
member of the panel and a professor of neurology at the University of
"I think this is a drug that needs further understanding with respect to
what it does to people's psyche," he says.
The panel's conclusion, in a 14-0 vote, throws up a major hurdle in a
longtime effort by its manufacturer to market the drug in the U.S. The decision
makes it unlikely that regulators will approve the drug for U.S. sales because
the FDA usually follows the recommendations of its advisory panels.
Studies conducted by its manufacturer, Sanofi-Aventis, show that many obese
patients can lose up to 10% of their body weight after one year on the drug. It
also appears to improve blood sugar control in obese diabetes patients.
In early 2006, the FDA was close to approving the drug, which at the time
carried the brand name Acomplia.
But the agency asked the company first to study reports that the drug seemed
to cause depression and suicidal thoughts and behaviors in some patients. It
also asked Sanofi-Aventis to abandon the name Acomplia because regulators
considered it potentially misleading to consumers.
The company responded by offering to minimize the risk by urging doctors not
to use the drug in patients with a history of depression or other mental
illnesses. In the process, the name Acomplia was changed to Zimulti.
Company officials clashed with regulators over the size of the psychiatric
risk, saying that thousand of patients who took the drug had suicide rates
essentially identical to the general population. Sanofi-Aventis said they'd
found a 30% increase in the risk of suicidal thoughts with the drug but that in
studies those thoughts almost never led to suicide attempts.
"The safety profile can only be interpreted in light of the demonstrated
benefits," Paul Chew, MD, Sanofi-Aventis' vice president for international
clinical development, told the committee.
But FDA scientists countered with an analysis of 13 studies showing that the
drug nearly doubled suicidal thinking while also doubling cases of anxiety,
depression, and other mood disorders.
Amy Egan, MD, an FDA safety official, says the agency had become worried
because the company excluded patients being treated for depression from its
Several prescription weight loss drugs are already on the U.S. market,
including Meridia and Orlistat. An over-the-counter version of Orlistat, known
as Alli, is set to hit store shelves this week.