Thursday, September 22, 2011

FDA Reviews Heart-Rhythm Drug Multaq -

Pressure is intensifying on U.S. regulators to take tougher steps on the Sanofi SA heart-rhythm drug Multaq, with many heart doctors saying they aren't prescribing the medicine in light of safety warnings and concerns about its effectiveness.
A European Medicines Agency committee is meeting this week to decide the fate of Multaq, while the U.S. Food and Drug Administration said Wednesday it is reviewing safety data and hopes "to soon update the public with more information."

Multaq is designed to treat a common form of aberrant heartbeat called atrial fibrillation, which afflicts millions of people. Once projected by analysts as a potential $1-billion-a-year drug, it has fallen short of the mark despite extensive marketing that included retaining singer Barry Manilow, who has suffered from an irregular heartbeat, as a consultant.

In interviews, several prominent specialists said they recommend against patients taking the drug. "It seems like it's not even safe in intermediate-risk patients," said Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center in Los Angeles. Dr. Kaul served on an FDA advisory panel about Multaq and voted in favor of approval, but he said he doesn't prescribe the drug.
Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, said, "I think the drug is dangerous." Louisville cardiologist John Mandrola said, "I'm surprised that the drug has persisted. I don't know any of my colleagues who would start a patient out on Multaq. It just doesn't work."

Doctors said they based their opinions both on published studies and their own clinical experience.
A Sanofi spokesman, Jack Cox, said the company "stands behind the importance of Multaq for patients with nonpermanent" atrial fibrillation. He said that 440,000 patients world-wide have been treated with it, and that Multaq "has a place in the treatment armamentarium."

Multaq is designed to reduce hospitalization for certain rapid heartbeats, in competition with a decades-old drug called amiodarone. The company says Multaq can reduce the risk of hospitalization.

It carries a boxed warning saying that the drug more than doubled the risk of death for the sickest heart-failure patients in one study, compared to placebo. Multaq shouldn't be given to such patients, especially if they have been recently hospitalized for cardiac reasons, the label says.
Sanofi's chief executive, Chris Viehbacher, said in a recent interview that the company continues to believe the drug has a favorable risk-benefit profile and that the company has had "positive" discussions with regulators. The FDA declined to make its latest safety analyses on Multaq available.
Multaq raised safety concerns at the outset because of the study suggesting a higher death rate. Two FDA reviewers wrote in 2009, before approval, that they were "concerned regarding the safety" of Multaq. The reviewers questioned the results of a second trial suggesting that the drug could ward off hospitalization, saying the standards for hospitalization can vary.
The drug's riskiness, they concluded, "presents a problem that the label alone may not be able to cover."
The FDA advisory panel backed the drug, finding it could help some patients, leading to approval by the FDA itself. Dr. Kaul said panel members "were struggling to find a patient population where it would not be unsafe." A transcript of the committee hearing confirms that members were wrestling with whether it was possible to distinguish patients who died from others who might benefit.
Sanofi's marketing has included paying consulting and other fees to 18 of 42 U.S. doctors on a cardiology societies' panel producing guidelines on how to treat atrial fibrillation, according to the published guidelines. Other big companies like Johnson & Johnson, Bayer AG, Bristol-Myers Squibb Co. and Medtronic Inc. all compete in different ways to treat A-fib, as it's called, and several drugs in the pipeline have billion-dollar-a-year potential, according to Wall Street analysts.
Multaq had world-wide first-half sales of €131 million ($179 million), according to Sanofi.

Early this year, the FDA ordered Sanofi to add in the label that "liver injury, including acute liver failure requiring transplant, has been reported in patients treated with Multaq." Another FDA letter to the company said that "postmarketing cases of new onset and worsening heart failure have been reported" with Multaq. In June, another Sanofi study showed a doubled rate of death and stroke, versus placebo, among moderately sick people who had permanent atrial fibrillation.
Write to Thomas M. Burton at


Christophe Kopp said...

In August 2010 the independent journal Prescrire wrote:
Dronedarone in atrial fibrillation: too many questions about long-term adverse effects

In patients with atrial fibrillation, dronedarone has less antiarrhythmic efficacy than amiodarone but fewer short-term adverse effects. Little is known of potential long-term adverse effects, but dronedarone has been linked to increased mortality in patients with heart failure.  When antiarrhythmic drug therapy is needed, it is better to continue to use a beta blocker or, as a last resort, amiodarone, a drug with better-documented adverse effects, especially during long-term treatment.

Christophe Kopp
Editor with Prescrire

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