Sanofi-Aventis plans to resubmit a new drug application to the FDA during the third quarter of 2008, for its atrial fibrillation (AF) drug Multaq, based on positive results of its ATHENA study.
The ATHENA study results, presented by Stefan Hohnloser, MD, at the Heart Rhythm Society (HRS) scientific sessions in San Francisco, showed that Multaq (dronedarone) significantly decreased the risk of cardiovascular hospitalizations or death from any cause by 24 percent, meeting the study’s primary endpoint, according to researchers. Results of the primary endpoint were consistent across all the pre-specified clinically relevant subgroups.
“Our prior [AF] treatment options have been focused only on symptom relief and a hope to not do harm, which has been the problem with prior antiarrhythmic drugs. Now, with a highly significant reduction in cardiovascular hospitalization or death, as well as a 45 percent reduction in arrhythmic death or 30 percent cardiovascular death, dronedarone may become an appropriate treatment option for atrial fibrillation,” said Christopher Cannon, MD, a senior investigator on the TIMI study at Brigham and Women’s Hospital, Harvard Medical School in Boston, who was not involved in the ATHENA study.
The researchers said that most frequently reported adverse events of Multaq versus placebo in the ATHENA study were gastro-intestinal effects (26 vs. 22 percent), skin disorders (10 vs. 8 percent, mainly rash) and increased blood creatinine (4.7 vs. 1 percent). The mechanism of blood creatinine increase (inhibition of creatinine secretion at the renal tubular level) was well-defined, in a separate study of healthy volunteers.
Researchers reported that Multaq showed a rate of pro-arrhythmia similar to placebo and no excess of hospitalizations for congestive heart failure. There was a similar rate of study drug discontinuation between the two study groups.
ATHENA, the largest double-blind randomized study in patients with AF conducted in more than 550 sites in 37 countries, enrolled a total of 4,628 patients.
The Paris-based Sanofi said that the ATHENA trial is the first morbidity-mortality study as part of the Multaq phase III clinical development program, which also included five other multinational clinical studies: an initial study, ANDROMEDA, conducted in patients with severe congestive heart failure and a recent decompensation, as well as a total of four international studies in AF: EURIDIS/ADONIS, ERATO and the ongoing DIONYSOS trial.
Sanofi also said it plans to submit a registration dossier to the European Medicines Agency.
Atrial fibrillation is a major cause of hospitalization and mortality and affects about 2.5 million people in the U.S., as well as 4.5 million people in the European Union.