Global Insight Perspective | |
Significance | The MHRA has reported 720 cases of adverse events and five deaths in people who were prescribed Sanofi-Aventis's obesity drug Acomplia since its U.K. launch in 2006. |
Implications | One of the deaths was a suicide, which is significant given Acomplia's reported links to psychiatric side-effects. However, none of the deaths have been conclusively linked to the drug. |
Outlook | Acomplia's risk profile is already well-established, and the MHRA may not choose to push for further restrictions on its use. However, the report will do little to assuage concerns over safety within the cannabinoid-1 receptor blocker class of weight-loss drugs. |
Deaths Reported Among U.K. Acomplia Users
The U.K.'s Medicines and Healthcare Products Regulatory Agency (MHRA) has published a report chronicling hundreds of adverse effects and five deaths in patients prescribed weight-loss drug Acomplia (rimonabant) since its market launch in 2006. The routine report highlights some 720 adverse reactions to the pill—produced by French pharma company Sanofi-Aventis—as well as one death by suicide. Two of the remaining deaths were caused by heart attacks, a third by infectious disease, while the remaining fatality was described by a Sanofi-Aventis spokesman simply as a "sudden death".
Acomplia was approved centrally in the European Union (EU) in June 2006, paving the way for its launch in the United Kingdom shortly thereafter (see France: 23 June 2006: European Approval Comes Early for Sanofi-Aventis' Acomplia). However, the following year brought an abrupt end to Sanofi-Aventis's dream of blockbuster sales for the obesity drug, when an advisory committee to the U.S. FDA refused to recommend its approval in light of data linking Acomplia to psychiatric adverse events (see France: 14 June 2007: FDA Advisory Committee Fails to Recommend Acomplia for U.S. Marketing Approval and France: 12 June 2007: Suicidal-Thoughts Link Threatens Sanofi-Aventis's Acomplia After New U.S. FDA Review). The company withdrew its U.S. marketing application for the drug and, combined with the failure to gain reimbursement status in other key markets such as Germany, the end result was that Acomplia's global sales remained muted. Total turnover for the drug in 2007 was 79 million euro (US$122.7 million).
Sanofi-Aventis Denies EU Anti-Trust Allegations
In a separate incident, anti-trust investigators from the EU have launched legal proceedings against Sanofi-Aventis, accusing the drug-maker of delaying a raid on its offices held earlier this year as part of a wider European inquiry into whether brand-name pharma companies were unlawfully preventing the entry of generic medicines on the EU market (see Europe: 17 January 2007: Big Pharma Marketing Practices Under Spotlight as EU Launches Competition Probe). According to U.K. newspaper The Times, the European Commission says that Sanofi-Aventis refused to surrender a document to anti-trust officials during the raid until a French judge had issued a warrant. The Commission is anxious to retain anti-trust powers at the EU rather than national level, and is within its rights to demand a fine of up to 280 million euro from Sanofi-Aventis If the firm is found guilty of non-cooperation. Sanofi-Aventis, for its part, has said that the allegation is false and insists that it has done everything possible to accommodate the investigation, which also involved AstraZeneca (U.K.), GlaxoSmithKline (U.K.), Pfizer (U.S.) and Novartis (Switzerland).
Outlook and Implications
The MHRA's report will come as a sobering reminder to Sanofi-Aventis that Acomplia is a drug that requires regular and high-level safety monitoring. Indeed, Acomplia features on the MHRA's list of marketed products that are "under intense surveillance", denoted by an inverse black triangle on their labelling. However, given that Acomplia's existing side-effect profile is already known, and that it is not possible to link deaths in post-marketing studies to the drug with 100% certainty, it is not guaranteed that the MHRA will take any more action on Acomplia in terms of further restricting its use. The report does, however, cast a shadow over a rival product currently in development by U.S. drug giant Merck & Co. Like Acomplia, taranabant is a cannabinoid-1 receptor (CBR1) blocker designed to promote weight loss, and Merck is hoping to file for U.S. FDA approval of the drug by the end of the year. However, with similar link to psychiatric side-effects already established, the chances of the FDA reacting favourably to taranabant after its dismissal of Acomplia are looking increasingly slim.
With regard to the EU anti-trust case, there is little doubt that the European Commission is trying to make an example out of Sanofi-Aventis as it attempts to strengthen European corporate law. The fine that potentially awaits the French pharma company is worth approximately 1% of its 2007 sales, but with few precedents existing for this type of case, it is unlikely that Sanofi-Aventis would have to pay the full amount. In the meantime, nothing has been proven against any of the drug-makers involved in the case, although EU anti-trust investigators recently announced they were broadening their investigations (see Europe: 15 May 2008: European Antitrust Investigators Probe Pharmaceutical Sector Over "Unfair" Competition).