Multaq phase 3 study halts; increased cardiovascular events cited

July 15, 2011

Dronedarone (Multaq, Sanofi), which is approved for nonpermanent atrial fibrillation (AF), was being tested on patients with permanent AF. However, that trial, PALLAS (Permanent Atrial fibrillation outcome Study using Dronedarone on top of standard therapy) phase 3b, has been terminated because it was causing increased cardiovascular events.

Dronedarone (Multaq, Sanofi), which is approved for nonpermanent atrial fibrillation (AF), was being tested on patients with permanent AF. However, that trial, PALLAS (Permanent Atrial fibrillation outcome Study using Dronedarone on top of standard therapy) phase 3b, has been terminated because it was causing increased cardiovascular events.

The decision to stop the study follows recommendations from the study’s Operations Committee and the Data Monitoring Committee and was not related to any hepatic adverse event, said a Sanofi press release.

Sanofi has informed regulatory authorities of this decision. The company also has asked all PALLAS clinical investigators to inform their patients participating in the trial to stop taking the study medication and consult their clinical trial centers. This direction applies to the PALLAS study patients only.

The benefit-risk of Multaq remains unchanged in its approved indication in nonpermanent AF. Patients currently taking Multaq should not stop their therapy and should consult their treating physician if they have questions.

The patient population included in the PALLAS study is different from the population for which Multaq is currently approved. In the PALLAS population, 70% of the 3,149 patients enrolled had permanent AF for more than 2 years; approximately 70% had NYHA heart failure Class I to III at baseline.

In contrast, in the study supporting the current indication (ATHENA), no patients enrolled had permanent AF and less than 30% of patients had NYHA heart failure Class I to III. PALLAS patients were also older than ATHENA patients.

To date approximately 400,000 patients have been treated with Multaq worldwide.

According to StopAfib.org, a patient-to-patient resource to help patients control their AF, as baby boomers continue to age, we can expect to see the AF epidemic worsen. Today AF affects more than 5.1 million people in the United States; that number is expected to climb to 15.9 million by 2050.

These numbers, from the Mayo Clinic, reflect only those patients with AF confirmed by an electrocardiogram and do not include many more who have symptoms but who cannot be confirmed. There also may be many more individuals who do not yet know they have the condidtion.

The increase in obesity and stress can be expected to accelerate the incidence of AF as well.