Less than a month after Sanofi discontinued a Phase IIIb trial in patients who were treated with its Multaq heart med due to a significant increase in cardiovascular events, regulators on both sides of the pond now say they are reviewing the merits of the controversial drug. Ironically, the study found a two-fold increase in death, and two-fold increases in stroke and hospitalization for heart failure.

The med is approved to reduce the risk of cardiovascular hospitalization in patients with persistent atrial fibrillation or atrial flutter who have had a recent episode and associated cardiovascular risk factors (here is the label). But the study was looking at people who suffer from permanent atrial fibrillation (see here). And so the study, called PALLAS, is now raising questions about the extent to which the drug can hurt the intended population.

“A critical question is whether and how the unfavorable results of the study, obtained in patients with permanent atrial fibrillation, apply to patients who use Multaq for the approved indications,” according to the FDA statement. Or as The European Medicines Agency puts it: “These new data could have an impact on the use of the medicine in its approved indication” (read this).

This is only the latest setback for Sanofi and its Multaq heart med, which is supposed to bolster its flagging fortunes as patent expirations near on its Taxotere cancer treatment and Plavix bloodthinner. Last month, French regulators reevaluated the effectiveness of the drug after two patients developed severe liver damage and decided Multaq is “insufficient,” which means French authorities could withdraw reimbursement (see this).

The EMA’s Committee for Medicinal Products for Human Use last January actually began a review following two cases of liver failure in patients on the drug that led to transplants. At the same time, the FDA issued a warning about the liver failures (see here).

Last year, by the way, a study in the Journal of the American College of Cardiology found the pill is only modestly effective and has no clear safety benefits (read here). And recently, questions were raised about the study in The New England Journal of Medicine that led to FDA approval and the extent to which Sanofi controlled the trial data (look here).

heart attack pic thx to bart on flickr