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Sanofi-Aventis’s worst fears have been realised with the news that a US regulator advisory panel has voted unanimously against recommending approval of the company’s obesity pill Acomplia® (rimonabant), leading to a share decline this morning of more than 6%.
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 14–0 against approving Acomplia, in combination with diet and exercise, for treating chronic obesity or for people who are overweight with at least one risk factor for heart disease. The panel said the benefits do not outweigh the risk of adverse effects seen in patients taking the drug, including suicide and seizures.
Sanofi issued a statement saying it plans to “work closely with the FDA to address the committee’s recommendations” before the agency makes its final decision, scheduled for 26 July. However, since the FDA hardly ever goes against the advice of its panels, there is pretty much zero likelihood of the drug hitting the US market – where it would have been sold as Zimulti – in the near future.
The committee reviewing the company’s application found that while 20mg of Acomplia did result in significant weight loss, people who took the treatment were twice as likely to have suicidal thoughts as those on placebo. Sanofi stated that three patients on the drug killed themselves during clinical trials, while a fourth suicide reported after the drug was approved in Europe in June 2006 has yet to be confirmed.
FDA staff medical reviewer Amy Egan said: “The numbers of events are small, but in aggregate they are worrisome.” She disagreed with the Franco-German drugmaker’s claim that the rise in cases of psychiatric adverse events was attributable to depression or other disorders not directly caused by Acomplia. “We strongly believe that it is causal,” she said, noting that 88% of patients who reported psychiatric problems when taking the treatment did not have a history of depression.
Sanofi had recommended that patients be screened for depression before being prescribed Acomplia and advised that patients should visit their doctors five times during the first year of treatment to be reassessed, but this did not convince the committee. Indeed, Ms Egan’s fears were echoed by panellist Prof Jules Hirsch, of New York’s Rockefeller University, who said: “There is a reasonable suspicion that we better learn some more and watch this affair more closely before we launch into use of the drug.”
The low likelihood of approval in the USA is a serious blow for Sanofi, which had hoped that Acomplia would be a blockbuster, and a big one at that, given that one-third of US adults are deemed clinically obese. The decision also suggests a hardening of attitudes at the FDA towards new drugs, especially in the present climate where the agency seems to be under constant attack from pressure groups and politicians who believe it has granted approvals far too easily in the past.