Sanofi-Aventis has pulled its Phase IIIb clinical trial comparing the efficacy of a 400 mg twice-daily dose of dronedarone (Multaq) to placebo in permanent atrial fibrillation (AF) patients after the PALLAS trial found an increase in cardiovascular (CV) event rates in the dronedarone arm. As a result, the European Medicines Agency (EMA) said that it will expand its review of the drug.
While the Paris-based Sanofi said that the drug benefits remained unchanged in the current patient population it is indicated to treat, non-permanent AF patients, the company said that decision was based off recommendations from the PALLAS trial’s operations committee and data monitoring committee (DMC).
Sanofi has informed authorities of its decisions, but said that patients currently prescribed dronedarone should not discontinue therapy and should consult their physicians with any concerns.
"Patient safety is of highest priority for Sanofi. We are notifying regulatory authorities in all countries where the product is approved or under review on this matter,” said Jean-Pierre Lehner, MD, Sanofi’s chief medical offficer. “We remain committed to Multaq as an essential treatment option for non-permanent AF patients.”
The randomized, double-blind, placebo-controlled PALLAS (Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy) trial enrolled 3,149 patients with permanent AF for over two years. Patients enrolled in the trial were over the age of 65 and had certain comorbidities such as systemic arterial embolism, MI, coronary artery disease, prior stroke or symptomatic HF, among others.
Major CV events and cardiovascular hospitalization or death from any cause were the trial’s primary endpoints.
In lieu of Sanofi’s decision to pull the trial, EMA has said that it will further review the drug’s cardiovascular risk after the discontinuation of the PALLAS trial. The agency's Committee for Medicinal Products for Human Use began a risk-benefit analysis of the drug in January. The agency said that it will determine whether further action is necessary at its meetings taking place July 18 through July 21.
Currently, dronedarone is approved in the European Union for patients with a history of non-permanent AF to prevent AF recurrence or to lower ventricular rate. In the U.S. the drug is indicated to reduce CV hospitalizations in patients with paroxysmal or persistant AF or atrial flutter.