Dronedarone Granted Reprieve

It seems Sanofi-Aventis's amiodarone analog drug, dronedarone (marketed as Multaq®), was granted a stay of execution by the FDA:

Multaq appeared at one stage to have little future, after an early clinical trial showed excess mortality and the drug was rebuffed by regulators.

As we recall:

Dronedarone is structurally similar to amiodarone but lacking the iodine moiety — a feature of amiodarone that has been linked to many non-cardiac side effects (including pulmonary toxicity, ocular effects, thyroid disease, and hepatic dysfunction). The Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) trial demonstrated the efficacy and safety of dronedarone in preventing AF recurrence after cardioversion in 199 patients. In the EURIDIS (European trial in atrial fibrillation or flutter patients receiving dronedarone for the maintenance of sinus rhythm) and ADONIS (American–Australian–African trial with dronedarone in atrial fibrillation or flutter patients for the maintenance of sinus rhythm) trials, dronedarone was effective in preventing AF recurrence and was shown to reduce the ventricular response during AF relapse. There was no evidence of proarrhythmia (including TdP), heart failure exacerbation, or thyroid, pulmonary, or other organ toxicity. The mortality rate was low (1.0%) and not significantly different from placebo (0.7%) during the 12-month follow-up. However, the Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) was stopped prematurely because of a trend towards increased risk of death in the dronedarone group, but this numerical increase in mortality was not statistically significant. In 2006, the United States Food and Drug Administration issued a non-approvable letter based on safety concerns. Consequently, the drug manufacturer withdrew an application for licensing to the European Agency for the Evaluation of Medicinal Products.

But new results from the Athena Trial (ppt) that excluded severe (Class IV) heart failure patients were favorable (except for some problems with a slight decline in renal function) suggesting the drug may become a promising new treatment for atrial fibrillation if approved by the FDA (decision expected in late January, 2009).

-Wes