The U.S. Food and Drug Administration has approved Sanofi's Multaq (dronedarone) 400 mg tablets for patients with atrial fibrillation or atrial flutter, marking the first drug approved in the United States that has demonstrated clinical benefit in reducing cardiovascular hospitalization for this patient population. The approval represents a significant milestone in a therapeutic area that has seen few new treatment options in the last twenty years.
Clinical Trial Results Drive Approval
The FDA approval is based on comprehensive data from five international, multi-center, randomized clinical trials involving nearly 6,300 patients, with over half receiving Multaq treatment. The landmark ATHENA trial, which evaluated 4,628 patients with atrial fibrillation or atrial flutter, demonstrated that Multaq reduced the combined endpoint of cardiovascular hospitalization or death from any cause by 24% (p<0.001) when compared to placebo, meeting the study's primary endpoint.
The clinical benefits extended beyond the primary endpoint. In the ATHENA trial, patients receiving Multaq experienced a 28% reduction in total hospital days compared to placebo and a 35% decrease in the total length of time spent in the hospital for heart-related reasons. These reductions were generally consistent across study subgroups based on baseline characteristics or medications.
Patient Population and Safety Profile
Multaq is indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter, with a recent episode 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 greater than or equal to 50 mm, or left ventricular ejection fraction less than 40%.
The drug carries important safety considerations. Multaq is contraindicated in patients with severe heart failure (NYHA class IV) or NYHA Class II-III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. This contraindication stems from results of the ANDROMEDA trial, which was terminated prematurely after enrolling 627 of 1,000 planned patients with congestive heart failure due to excess mortality in the dronedarone group (25 versus 12 deaths with placebo, p=0.027).
Risk Mitigation and Market Impact
To ensure appropriate patient selection, Sanofi has launched mPACT (Multaq Partnership for Appropriate Care and Treatment), a Risk Evaluation and Mitigation Strategy developed to assist healthcare professionals with patient identification and ensure safe use while minimizing risk. The program consists of a communication plan for healthcare professionals, a medication guide for patients, and post-marketing surveillance.
The most common adverse reactions observed in clinical trials include diarrhea, nausea, vomiting, abdominal pain, weakness, and cutaneous rash. Patients taking Multaq also showed higher rates of bradycardia and QT-interval prolongation compared to those receiving placebo.
Addressing Significant Medical Need
Atrial fibrillation affects approximately 2.5 million people in the United States and 4.5 million people in the European Union, with incidence growing worldwide in relation to aging populations. The condition is emerging as a public health concern and represents the leading cause of hospitalization for arrhythmia in the U.S., accounting for one-third of arrhythmia hospitalizations in Europe.
"The FDA approval of Multaq is an important milestone in the management of atrial fibrillation or atrial flutter that demonstrates the commitment of sanofi-aventis to provide patients and physicians with important new medicines in therapeutic areas with significant healthcare needs," said Christopher A. Viehbacher, Chief Executive Officer of sanofi-aventis.
Stuart Connolly, Professor of Medicine and Director of the Division of Cardiology at McMaster University and co-principal investigator in the ATHENA study, noted the significance of the approval: "It is exciting that Multaq will now be available as a treatment option for patients with paroxysmal or persistent atrial fibrillation or atrial flutter. Based on clinical studies, Multaq reduces the risk of cardiovascular hospitalizations in patients with atrial fibrillation/atrial flutter, this outcome could change the way we approach the management of the disease."
Treatment Administration
Multaq is administered as a 400 mg tablet taken twice daily with morning and evening meals. Treatment can be initiated in an outpatient setting, providing flexibility for patient management. The drug is also under regulatory review by the European Medicines Agency.
Sanofi has predicted annual sales of more than 1 billion euros for Multaq, though analysts believe this estimate may be conservative given the drug's position as the first new treatment option to emerge from Sanofi's pipeline in an extended period and the significant unmet medical need in atrial fibrillation management.
