In a session at Boston AF that focused on the recent trials (and tribulations) of dronedarone (Multaq, Sanofi-aventis), Peter Kowey (Lankenau Medical Center and Institute of Medical Research, and Jefferson Medical College, Pennsylvania, USA) declared that the recent failure of the PALLAS study did not mean that they were “throwing in the towel” with dronedarone and announced plans for a new dronedarone study.
HARMONY, Kowey told delegates attending Boston AF, is an “extremely interesting” study that will review a new combination of dronedarone and ranolazine (Ranexa, Gilead Sciences) in lower doses. He said: “This combination is off the chart. It is one of the most effective drugs we have seen in the pre-clinical models that we have used for atrial fibrillation. We are very enthusiastic that these two drugs, in combination, will have an effect.”
He explained that the design of the study will be like the design of the PASCAL study (Ezekowitz et al, J Interv Card Electrophysioly 2011; Epub), which investigated three doses of budiodarone (Aryx Therapeutics) in patients with paroxysmal atrial fibrillation and who had implanted pacemakers. Similarly, HARMONY will investigate the combination of dronedarone and ranolazine to reduce the burden of atrial fibrillation in patients with pacemakers. The HARMONY investigators are hoping to enrol 150 patients at 45 sites in North America and in Europe. Kowey said that they are looking for more centres and he asked the delegates of Boston AF to contact him if they wanted to become involved.
HARMONY is not the only reason that dronedarone’s story will continue. While the results of the PALLAS study, which showed dronedarone to be associated with an increased risk of death in patients with permanent atrial fibrillation, and other negative findings have led to new restrictions on the use of dronedarone in both Europe and America, it will continue to be on the international market. Kowey said: “I think this is appropriate. One of things that the Europeans [European Medicines Agency] said in the prelude to their new labelling for dronedarone was that we do not have many options to treat atrial fibrillation, so maybe we should not write this one off completely.” He added that he continued to use dronedrone-albeit much more selectively and with closer monitoring. He said: “It was initially promised as a much simpler drug than existing antiarrhythmics that primary care doctors could prescribe, but that is not going to be realised. It should be restricted to cardiologists and electrophysiologists, who can monitor it for safety and efficacy. But, we are not going to give up. Hopefully over the next few years, we will continue to develop antiarrhythmic drugs that are safe and effective for this indication.”
