IHS Global Insight Perspective | |
Significance | A senior FDA reviewer has recommended U.S. approval for Sanofi-Aventis's Multaq (dronedarone) for atrial fibrillation, but not for atrial flutter, and has excluded patients with severe heart failure from being prescribed the drug. Sanofi-Aventis should also not claim that Multaq can reduce risk of death, the reviewer said. |
Implications | If Multaq is approved along these lines, it would still be available for the majority of the patient population aimed at by Sanofi-Aventis. However, the company may need to take steps to prove to the FDA that Multaq's prescribing will remain restricted to the appropriate patients. |
Outlook | Multaq is likely to be approved by the FDA, albeit with some restrictions, and the approval will be a critical turning point in Sanofi-Aventis's bid to reassure investors of its long-term commercial viability. |
The U.S. FDA's leading reviewer of cardiovascular and renal drugs has given tentative backing to French pharma company Sanofi-Aventis's drug Multaq (dronedarone). In a memo to the FDA's Cardiovascular and Renal Drugs Advisory Committee, lead reviewer Abraham Karkowsky recommended that Multaq should be approved as a means of delaying the symptoms of atrial fibrillation, and reducing hospitalisation triggered by the condition. However, Karkowsky also said that certain limits should be imposed on the approval, namely that the approved indication should be limited to atrial fibrillation, and exclude atrial flutter—a smaller patient population that Sanofi-Aventis had also been focusing on in Multaq's application to the FDA—and patients with severe heart failure. The memo also said that Sanofi-Aventis should not be allowed to make claims as part of its marketing that Multaq lowers the risk of death.
Multaq will be the subject of a separate review held tomorrow by an outside panel of medical experts appointed by the FDA. The FDA itself is expected to make a final decision on Multaq by the end of April. It will be the second time the FDA has had to decide on whether to approve Multaq, following its rejection of the drug in 2006. At the time, the FDA said its decision was based on a clinical trial that had been halted in 2003, after it was seen that patients with severe heart failure receiving Multaq were at a higher risk of death than those taking a placebo.
Karkowsky's memo makes reference to this 2003 trial, using it as the main reason why Sanofi-Aventis should not be permitted to claim that Multaq lowers patients' risk of death. The memo also claims that the company had significantly modified and expanded the remit of a later clinical trial used in the second FDA application to demonstrate a reduction in mortality brought on by Multaq. Finally, Karkowsky says that Sanofi-Aventis has not presented sufficient clinical evidence to show that Multaq can successfully treat patients with atrial flutter, which is why the drug's approved indication should be limited to atrial fibrillation. The FDA memorandum can be viewed in full here.
Outlook and Implications
Multaq's approval by the FDA is of critical importance to Sanofi-Aventis, which has blockbuster expectations for the drug. Peak annual sales predictions for Multaq have been estimated at US$1.8 billion to US$2 billion, while it has been suggested that the drug could eventually reach gold-standard first-line status as an atrial fibrillation drug.
From the company's point of view, securing regulatory backing for such a potentially successful drug is more important than ever, as Sanofi-Aventis's two current highest sellers—cardiovascular drugs Lovenox (enoxaparin sodium) and Plavix (clopidogrel bisulphate)—are approaching patent expiry in the United States, and no new potential Sanofi-Aventis blockbusters have been approved in the United States in over a decade. Although the French pharma giant is looking to bolster top-line growth through acquisitions, shareholders also need to be reassured over the commercial viability of its in-house research and development pipeline, and U.S. backing for Multaq would be the best way of demonstrating this (see France: 11 February 2009: Acquisitions Central to Future Growth as Sanofi-Aventis Reveals 1.7% Y/Y Loss in 2008 Sales).
IHS Global Insight believes that Multaq will see FDA approval the second time around, albeit in a slightly reduced patient population. Sanofi-Aventis is likely to be called on to develop a Risk Evaluation and Mitigation Strategy for the drug, in order to allay FDA concern over the potential for Multaq being prescribed off-label to patients with more than mild levels of heart failure.