Sanofi has suffered a setback in its bid to get expanded use of Multaq with the news that a Phase IIIb trial of the anti-arrhythmic has been stopped.
The French drugmaker has discontinued the PALLAS trial in patients with permanent atrial fibrillation, different from the population with non-permanent AF for which Multaq (dronedarone) is currently approved. The decision follows recommendations from the study’s operations committee and the data monitoring committee which observed "a significant increase in cardiovascular events in the dronedarone arm".
In the PALLAS population, 70% of the 3,149 patients enrolled had permanent AF for over two years. This contrasts with the study that supported the approved indication (called ATHENA) where no patients had permanent AF and Sanofi notes that PALLAS patients were also older than those on the ATHENA trial.
No liver problems
The Paris-based drugmaker added that the decision to terminate the study was not related to any hepatic adverse event. Multaq has been linked to serious liver damage and its safety is under review by European regulators; earlier this year, the US Food and Drug Administration added an extra warning on its label about the potential risk of liver injury.
Sanofi is clearly disappointed but chief medical officer Jean-Pierre Lehner said that "patient safety is of highest priority". He added that the company is notifying regulatory authorities in all countries where the drug is approved or under review about this matter, stating that “we remain committed to Multaq as an essential treatment option for non-permanent AF patients".
Some 400,000 patients have been treated with Multaq, which was approved in Europe and the USA in 2009. Sales of the drug have not been spectacular to date, 63 million euros in the first quarter of 2011, and analysts hoped that getting approval for the permanent AF indication would have provided a major boost to revenues.