Sanofi, maker of dronedarone (Multaq), has suspended its phase 3b trial of its antiarrhythmic drug due to an increase in cardiovascular events seen in patients randomized to dronedarone. The PALLAS trial was testing the drug in patients with permanent atrial fibrillation (AF) and at least one other cardiovascular disease risk factor; at present, dronedarone is approved in patients with nonpermanent AF.
The trial’s operations and data monitoring committees made the decision to halt the study after seeing a significant increase in cardiovascular events among patients taking the study drug, as compared with patients on placebo, although details of just what those events are have not been released. In both arms of the trial, patients were also receiving antithrombotic and rate-control medications.
According to a press release issued by Sanofi on July 07, 2011, the company has informed regulators about the decision to stop the trial and asked trial investigators to get in touch with patients to tell them to stop taking the drug. Patients taking Multaq outside of the trial, however,
Of note, the press release states that the “decision to terminate the study was not related to any hepatic adverse event.” Liver injuries are a known side effect of the drug and have previously prompted warnings by both US and European regulators.
PALLAS was launched in July 2010 and was designed to enroll 10 800 patients, with an estimated completion date of August 2013. Only 3149 patients had been enrolled at the time the study was stopped. The study was to include over 585 sites, and according to Connolly, those included 185 sites in the US and at least 20 in Canada.
Dronedarone has faced a range of criticisms since its approval in the US in July 2009, including questions about its safety/efficacy tradeoff and the design and execution of the ATHENA study. Just last week, newspapers in France reported that French health authorities had concluded that the efficacy of dronedarone was “insufficient”—an opinion that could lead to the drug being dropped from the country’s drug reimbursement formulary.
Source: the heart.org