FDA Approves dronaderone for patients with Atrial Fibrillation or Atrial Flutter

It has recently been announced that the U.S. Food and Drug Administration (FDA) has approved the use of dronaderone (Multaq®) for patients with atrial fibrillation (AF) or atrial flutter (AFL). Multaq® is the first drug approved in the United States that has shown a clinical benefit to reduce cardiovascular hospitalization in patients with AF/AFL.

Dronaderone is an anti-arrhythmic indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted. Associated cardiovascular risk factors include age over 70 years, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction [LVEF] <40%. The FDA approval is based on five international, multi-center, randomized clinical trials involving nearly 6,300 patients.

The landmark ATHENA trial evaluated the efficacy and safety of dronaderone in patients with AF/AFL or a recent history of these conditions (71% of these patients had no heart failure, 29% were in NYHA class I-III with stable heart failure). This trial showed that dronedarone 400 mg BID, in addition to standard therapy, by 24% (p<0.001) when compared to placebo, meeting the study’s primary endpoint.

This reduction was generally consistent across study subgroups based on baseline characteristics or medications. Patients taking dronaderone had higher rates of diarrhoea, nausea, bradycardia, QT-interval prolongation and cutaneous rash than patients taking placebo.

Initiation of dronaderone treatment is contraindicated in patients with severe heart failure (NYHA class IV) or NYHA Class II – III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. This unstable population corresponds to the population of the ANDROMEDA trial in which patients receiving dronedarone had a greater than 2-fold increase in mortality compared to placebo.

The ATHENA and ANDROMEDA trials provided two sets of data supporting the assessment of the product’s benefit risk ratio in two significantly different patient populations.

To ensure the use of dronaderone in the appropriate patient population, the manufacturers, sanofi-aventis U.S. LLC also announced the launch of mPACT™ – Multaq^® Partnership for Appropriate Care and Treatment-the Risk Evaluation and Mitigation Strategy (REMS) developed by sanofi-aventis US.LLC. The mPACT™ Partnership was developed to assist health care professionals (HCPs) with the identification of appropriate patients and to ensure the safe use of Multaq while minimizing risk. The risk mitigation programme consists of a Communication plan for HCP, a medication plan for patients and post-marketing surveillance.

A registration dossier of Multaq^® is also under regulatory review by the European Medicines Agency (EMEA).

For full prescribing information, please visit http://products.sanofi-aventis.us/Multaq/Multaq.pdf