Global Insight Perspective | |
Significance | A 20-mg dose of Sanofi-Aventis's weight-loss drug Acomplia has been linked with a higher incidence of suicidal thought and behaviour than placebo in an FDA review of all trials on the drug to date. |
Implications | The review also found that the drug unquestionably led to significant and consistent weight loss at the same dose. However, the news has broken just ahead of a meeting by the FDA's advisory committee, which is meant to recommend whether or not to approve Acomplia/Zimulti in the U.S. |
Outlook | Acomplia's weight-loss benefits and its existing marketing status in both Europe and South America form a solid case for its approval in the United States. However, with the FDA under increasing scrutiny for regarding patient safety, a request for further trials is still possible, causing yet more delays to Sanofi's potential blockbuster U.S. sales. |
A safety and efficacy review of weight-loss drug Acomplia (rimonabant) has uncovered statistically significant levels of adverse psychiatric events associated with consumption of the product. Acomplia is produced by French pharmaceutical company Sanofi-Aventis, which submitted a dossier of clinical findings to the U.S. FDA last October. Upon compiling these, the FDA said in documents released last night that specifically, some 9% of patients treated with the 20-mg dose of Acomplia reported symptoms of depression, compared with just 5% of patients given placebos. More disturbingly, a meta-analysis of some 13 clinical trials conducted by Sanofi-Aventis found that a greater number of events linked to "suicidality"—suicidal behaviour and thought rather than actual suicide—were recorded among patients taking the 20-mg dose than those taking the 5-mg dose or those administered placebos. More specifically, some 46 separate incidences of suicidal thought or behaviour were recorded in the Acomplia 20-mg group, compared with eight in the 5-mg group and 20 in the placebo group. There were, however, more cases of attempted suicide in the placebo group (seven) than in the Acomplia 20-mg group (four).
Sanofi-Aventis submitted its clinical trial information on Acomplia to the FDA last year in order to relaunch its attempts to gain regulatory approval to market the drug in the United States. A first attempt, made in 2005, was thwarted early the next year, as the FDA issued an approvable letter to Sanofi-Aventis (see France: 20 February 2006: U.S. FDA Deals Blow to Sanofi-Aventis with Approval Delay for Weight-Loss Drug). Now, following the release of this latest review, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee is due to meet tomorrow in order to discuss the drug's safety and efficacy. Once the committee comes to a decision as to whether Acomplia—to be marketed under the brand name Zimulti in the United States if approved—should be given the regulatory green light, the FDA must then make a final verdict on the issue. The FDA is not obliged to follow the recommendation of its advisory committee, but has often done so in the past.
Outlook and Implications
In documents released on its website, the FDA hints that questions of "suicidality" lay behind its original approvable letter in February 2006, leading to more than a year's delay before the impending advisory committee review. These questions have obviously remained at the forefront of the FDA's concerns, although the organisation has also conceded that the 20-mg dosage was "associated with statistically and clinically significant weight loss". This, combined with the fact that Acomplia has been approved in the European Union (EU) since mid-2006 and is now on sale in several EU member states as well as in Brazil and Argentina, should still make a pressing case for the drug's approval in the United States.
It is entirely, possible, however, that the FDA will demand yet more clinical trials to ensure that maximum safety precautions have been taken, particularly as other innovative weight-loss treatment options are becoming increasingly available. U.K. pharma heavyweight GlaxoSmithKline's OTC obesity drug Alli (orlistat) is set for its U.S. market debut next week, and is expected to make a big impact (see United Kingdom: 12 June 2007: GSK to Roll Out First OTC Obesity Drug in U.S. as FDA Seeks More Data on Bowel Drug).
In Europe, conversely, national drug regulatory agencies may now be inclined ask Sanofi-Aventis for similar data on adverse psychiatric events, particular those linked to suicide, in order to potentially review the drug's labelling. This remains a relatively minor possibility, however, as European regulators would have been privy to the same clinical trial data as their U.S. counterparts. For Sanofi-Aventis, the prospect of a further delay to U.S. marketing for Acomplia/Zimulti would mean yet longer to wait before a new potential blockbuster emerges to take the heat off blood-thinner Plavix (clopidogrel bisulfate) as it battles against generic competition (see France: 3 May 2007: Brighter Outlook Predicted as Sanofi-Aventis's Q1 Sales Start to Bounce Back).