Sanofi to Resubmit Heart Drug
To FDA as New Data Emerge
By PETER LOFTUS
June 19, 2008; Page D5
An experimental heart drug from Sanofi-Aventis more than doubled the risk of death in people with heart failure in a study that was terminated early in 2003 due to safety concerns.
Sanofi still plans to resubmit the drug, dronedarone, for regulatory approval in the U.S. and Europe by the end of September because a more recent study suggested the drug reduced the risk of death in patients with a heart condition known as atrial fibrillation, or irregular heartbeat. In 2006, the U.S. Food and Drug Administration rejected the drug, which Sanofi proposes to market under the brand Multaq. "I would say a majority of patients would be eligible for this treatment," said Paul Chew of Sanofi's research-and-development unit.
But even if Sanofi gets the regulatory green light to market Multaq, the newly published data suggest it shouldn't be used by people with severe heart failure because it appears to worsen heart failure. That could limit its market potential. Sanofi has predicted the drug could generate annual sales of more than $1 billion.
Paris-based Sanofi said in January 2003 that it terminated the "Andromeda" study of Multaq in people with congestive heart failure and ventricular dysfunction. Heart failure involves a weakened heart that causes fatigue and shortness of breath. An independent safety committee monitoring the study said at the time there was a potential excess risk of death in patients taking Multaq.
Five years later, the full results of the Andromeda study are being published online Wednesday by the New England Journal of Medicine. They show that 25 of about 310 people who took Multaq died after two months, versus 12 deaths among 317 people taking a fake drug, or placebo. The rates of death were 8.1% in the Multaq group, versus 3.8% in the placebo group.
Sanofi developed Multaq as a so-called antiarrhythmic drug to treat atrial fibrillation, which affects about 2.2 million Americans and 4.5 million people in the European Union, according to figures from the American Heart Association and Sanofi. Atrial fibrillation can lead to stroke.
A common treatment for atrial fibrillation includes an older, generic drug called amiodarone, but it is associated with side effects such as damage to the lung and liver, and muscle weakness. Sanofi's Multaq was designed to have equal or better effectiveness than amiodarone, but with less severe side effects.
Sanofi tested Multaq in people with heart failure partly because people with that condition have an increased risk of atrial fibrillation, and it can contribute to the death of heart-failure patients.
The company had planned to study 1,000 people who were hospitalized with symptomatic heart failure and a condition known as severe left ventricular systolic dysfunction, with about half receiving Multaq and the other half getting a placebo. Some 627 patients in Europe were enrolled at the time of the study's termination in 2003.
Among those who died during the study, 10 Multaq users had worsening heart failure, versus only two with worsening heart failure in the placebo group. This suggests the possibility that Multaq contributes to worsening heart failure, researchers said.
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