A potential blockbuster took a big step closer to market last week as FDA approved Sanofi-Aventis’ atrial fibrillation treatment Multaq (dronedarone).
The approval represented a comeback for the drug, which was rejected by FDA three years ago over safety concerns. In one of its clinical trials, called Andromeda, Multaq not only failed to benefit patients suffering from severe heart failure, but also increased overall mortality.
That may sound like a good reason to shelve a drug, but Sanofi instead set scientists to work figuring out what had gone wrong.
“Based on the Andromeda study, we were able to examine the data and see what sort of patients should not get Multaq, and that was the basis of starting the Athena trial,” said Paul Chew, chief science officer and chief medical officer for Sanofi-Aventis US.
Rather than focus on patients suffering from severe heart failure, Sanofi decided to examine atrial fibrillation (AF)—an irregular rhythm in the upper chamber of the heart found in adults and the elderly, which leads to blood clots and possibly strokes. Patients with the disease have an increased risk of hypertension, high blood pressure, and an associated risk of heart attack.
Until now, the most commonly used therapy for AF has been amiodarone—a drug that is not approved for the indication, and only reluctantly approved at all by FDA because of its potentially significant side effects: pulmonary fibrosis, hyperthyroidism, tremors, and severe skin rash. Amiodarone also has a two-month half-life, an undesirable quality in a drug with a high side-effect profile. Multaq, by comparison, has a half-life of 24 hours.
In the subsequent Athena study, Sanofi eschewed patients with severe heart failure and focused on patients with AF and few or no instances of heart failure. Multaq was found to have a 24 percent combined endpoint reduction in mortality and cardiovascular hospitalization, when compared to placebo. The drug was also found to have a very good safety profile, with only a few GI side effects.
“This data should help Multaq gain share,” stated an analyst for Zacks Equity Research, in a report. “We expect the product to contribute significantly to revenues and believe it could eventually achieve blockbuster status. Multaq should reach the €500 million mark in 2012.”
The company resubmitted the NDA in 2008, and was approved by an FDA advisory panel earlier this year. Sanofi is now gearing up for a summer launch and is developing additional clinical trials for the drug. No word yet on marketing strategy.