Dronedarone approved in the European Union for patients with atrial fibrillation


Sanofi-aventis announced on 30 November 2009 that the European Commission has granted marketing authorisation for Multaq (dronedarone, 400mg tablets) in all 27 European member states. This approval follows the European Commission positive opinion issued on 25 September 2009 by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicine agency (EMEA).

Multaq is indicated in adult clinically stable patients with a history of, or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate. Multaq, discovered and developed by sanofi-aventis, is the first anti-arrhythmic drug approved in the European Union that has shown a clinical benefit to reduce cardiovascular hospitalisations or death from any cause in patients with AF/AFL as described in the ATHENA trial.

“The approval of Multaq in the European Union is important news for atrial fibrillation patients who will now have access to a new treatment approach,” said Marc Cluzel, executive vice president, Research and Development, Sanofi-aventis. “The approval of Multaq is the result of more than 15 years of research and development conducted by Sanofi-aventis and supported by the commitment of the experts involved in the clinical development program and AF patients participating in the trials.”

The use of dronedarone in unstable patients with NYHA class III and IV heart failure is contraindicated. Because of limited experience in stable patients with recent (1 to 3 months) NYHA class III heart failure or with left ventricular ejection fraction (LVEF) <35%, the use of Multaq is not recommended in these patients.

The marketing authorisation of Multaq was based on the review of a comprehensive clinical data package including seven international, multicentre, randomised clinical trials involving more than 7,000 patients with almost 4,000 patients receiving dronedarone during the clinical development program.

“This European approval is good news for doctors and patients since atrial fibrillation affects about 4.5 million people in Europe and represents one-third of hospitalisations for arrhythmia in the European Union” said Stefan H Hohnloser, JW Goethe University’s Division of Clinical Electrophysiology, Frankfurt, Germany, principal investigator of the ATHENA study. “Multaq is a significant step forward which could change the way we approach the management of atrial fibrillation and offers a new treatment option to physicians in a field where there has been no significant anti-arrhythmic drug innovation for almost 20 years.”

The first launches of Multaq are expected to take place in the United Kingdom and Germany in January 2010. Multaq is already approved in the United States, Canada, Switzerland and Brazil.

About Multaq

The marketing authorisation of Multaq was based on the review of four placebo controlled studies in patients with AF or atrial flutter (AFL) called EURIDIS, ADONIS, ERATO and ATHENA; the DIONYSOS trial, a comparative trial vs. amiodarone; and the ANDROMEDA trial, a placebo controlled study in heart failure patients with a recent hospitalisation for decompensated systolic heart failure.

The landmark ATHENA trial was the largest anti-arrhythmic drug trial ever conducted in patients with AF/AFL, involving 4,628 patients with a follow-up of 30 months. In this trial, dronedarone, on top of standard therapy, significantly reduced cardiovascular hospitalisation or death by 24 percent when compared to placebo, meeting the study’s primary endpoint. This reduction was generally consistent across study subgroups based on baseline characteristics or medications.

The most common adverse reactions were diarrhoea, nausea, vomiting, abdominal pain, asthenia (weakness) and skin rash.

Dronedarone has a convenient fixed dose regimen of twice daily 400mg tablets to be taken with morning and evening meals. Treatment with dronedarone does not require a loading dose and can be initiated in an outpatient setting with minimal monitoring.

The EURIDIS-ADONIS, ANDROMEDA and ATHENA trials were published in the New England Journal of Medicine respectively in 2007, 2008 and 2009.