Sanofi’s Multaq, approved to treat patients whose hearts intermittently race with quick and inefficient contractions, doubled the risk of death in those with a permanent form of the erratic rhythm, a study found.
Stroke and heart failure rates also rose significantly in those given Multaq during the trial of 3,236 patients, a blow for the drug that doctors thought would avoid the risks seen with earlier generations of anti-arrhythmic drugs. The research was halted in July because of the increased danger, and the results were presented today at the American Heart Association’s annual meeting in Orlando, Florida.
Doctors had hoped the drug’s ability to reduce deaths, strokes and hospitalizations in patients with occasional atrial fibrillation would carry over to those with the more serious form of the condition, said lead researcher Stuart Connolly, from the Population Health Research Institute in Hamilton, Ontario. The findings shoot down the hypothesis, he said.
“We have had a healthy suspicion of anti-arrhythmic drugs for many years, but we had thought this drug didn’t have the same risks,” Connolly said in a telephone interview. “We are now getting the message that this drug has the potential to harm as well,” he said. “It seems this drug acts very differently depending on which type of patient receives it.”
The study, funded by Paris-based Sanofi, was published in the New England Journal of Medicine. There were 21 deaths from cardiovascular causes in the Multaq group, compared with 10 among those getting placebo.
A separate trial of Sanofi’s celivarone, a once-a-day drug thought to be a potential successor to Multaq, failed to prevent sudden deaths and inappropriate electrical shocks in heart patients with implanted defibrillators. The study was halted in July and the company has discontinued the drug’s development.
The results shouldn’t change the use of Multaq for patients with intermittent atrial fibrillation, said Deepak Bhatt, chief of cardiology at the VA Boston Healthcare system and director of the interventional cardiovascular program at Brigham and Women’s Hospital in Boston. Instead, the research will focus the drug’s use among doctors who are allowed to prescribe medicines even for conditions where they aren’t specifically approved, he said.
“Often doctors are doing things based on a hunch or an anecdote,” Bhatt said in a telephone interview. “In the right patient, this drug can be useful, but the broader use in high-risk patients, that clearly isn’t going to happen,” he said.
The drug, once expected to generate $1 billion in annual sales, was approved in 2009. The medicine had sales of $237 million last year, and analysts have cut their estimates since September after European regulators said it should only be given to those who don’t benefit from alternatives because it boosts the risk of cardiovascular, liver and lung injuries.
“Multaq isn’t dead but it won’t be the drug we were hoping for,” Pierre Corby, an analyst at Aurel BCG in Paris who recommends buying Sanofi shares, said in a telephone interview. Corby says he plans to lower his peak annual sales estimate on Multaq, which stands at 500 million euros ($680 million) by 2015.
The U.S. Food and Drug Administration is reviewing Multaq’s safety profile.