Post-Market Clinical Trial for Multaq Halted amongst Concerns

Washington, DCA clinical trial designed to assess the effectiveness of a drug to treat abnormal heart rate has been stopped early following a discovery by a data-monitoring committee of a two-fold increase in death, according to a communiqué from the US food and Drug Administration (FDA). The drug agency is reviewing the data from Multaq, manufactured by Sanofi Aventis—as is Health Canada north of the border.

Multaq (dronedarone) is prescribed to patients suffering from permanent atrial fibrillation. According to a posting by the Canadian Broadcast Corporation (CBC) late last night, the post-market trial for a drug already approved and on the market had been attempting to evaluate the effectiveness of Multaq for use in patients over the age of 65 with an abnormal heart rate. Multaq, it was thought, would reduce the risk of hospitalization for such patients.

The reality, according to a release dated July 21 from the FDA, is that Multaq not only appeared to be associated with a two-fold increase in death—there were also corresponding two-fold increases in stroke and hospitalization for heart failure…the very event the drug was designed to ward against.

It should be noted that Multaq was approved by the FDA based on the results of the ATHENA trial, and was given the agency's blessing for patients with related cardiovascular issues; among them, patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted.

The latest study, dubbed Permanent Atrial fibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy, or PALLAS, was an attempt to assess the drug for a new indication.

That indication is now in doubt, while the FDA urges patients currently prescribed Multaq for the approved indication to seek learned counsel from their doctor as to the wisdom or need for continuing with Multaq for the approved indication in spite of the early termination of the PALLAS trial. The FDA noted it was important for Multaq patients having concerns to avoid taking matters into their own hands and stopping the medication without first consulting with a medical professional.

It's been two years this month that Multaq has been on the market, after it was approved by the FDA and Health Canada in July 2009. Since then, according to information from the FDA, Multaq has been prescribed about a million times to 241,000 patients.

So far, neither health authority is prepared to do anything beyond issuing a caution about the drug and digging into the data mined from the halted PALLAS trial. Health Canada, according to the CBC, did issue a previous warning in tandem with Multaq manufacturer Sanofi with regard to the potential for risk of liver injury