FDA's advisory panel votes against approval of Medtronic Phased RF Ablation System

Medtronic, Inc. (NYSE: MDT) today announced that the U.S. Food and Drug Administration's (FDA) Circulatory Systems Devices advisory panel voted against the Medtronic Phased RF Ablation System, the first atrial fibrillation ablation therapy under investigation for the treatment of persistent and long-standing persistent atrial fibrillation. While the panel unanimously agreed the technology is effective, the majority did not believe there is reasonable assurance of the safety of the Medtronic Phased RF Ablation System, and that the clinical benefits of the technology do not outweigh the potential risks based on the TTOP-AF clinical trial data.

Today's committee recommendation, although not binding, will be considered by the FDA as it reviews the pre-market approval application for the Medtronic Phased RF Ablation System. Medtronic submitted a modular pre-market approval (PMA) application with the last submission completed in June 2011 based on data from its pivotal TTOP-AF (Tailored Treatment of Persistent Atrial Fibrillation) clinical trial, the first randomized study comparing ablation therapy to traditional medical management (antiarrhythmic drugs and direct current cardioversion) in patients with persistent or long-standing persistent atrial fibrillation.

"While we are disappointed with today's outcome, Medtronic looks forward to continuing discussions with the FDA to determine the best path forward," said Reggie Groves, vice president and general manager of Medtronic's AF Solutions business. "We believe this technology would represent an important option for the persistent or long-standing persistent atrial fibrillation population, for whom treatment is limited."

Currently, the only FDA approved atrial fibrillation ablation medical devices are indicated for the treatment of paroxysmal atrial fibrillation, a type of disease in which irregular heartbeats in the upper chambers start and stop suddenly on their own, usually for minutes or days at a time. As the disease progresses into persistent (recurrent episodes that last more than 7 days) or long-standing persistent (continuous episodes that last more than one year) atrial fibrillation, it becomes more complex to treat. Persistent atrial fibrillation patients often have increased hospitalizations and healthcare costs, and the condition is more debilitating in terms of quality of life.

Results from the TTOP-AF clinical trial were presented on October 10, 2011 at Venice Arrhythmias 2011, the 12th International Workshop on Cardiac Arrhythmias. The study met its chronic effectiveness endpoint, demonstrating that 55.8 percent of patients treated with the Medtronic Phased RF Ablation System had an atrial fibrillation and atrial flutter burden reduction of greater than 90 percent and were free from antiarrhythmic drug therapy at six months, compared to 26.4 percent in the traditional medical management arm (p<0.0001). When including patients still on antiarrhythmic drug therapy following the procedure with the ablation system, 67.4 percent had a greater than 90 percent reduction of atrial fibrillation burden at six months.

The acute safety event rate in the trial was 12.3 percent with an upper 95 percent confidence interval of 19 percent, which did not meet the pre-defined performance goal of 16 percent. At the time the trial was designed, no benchmark for the persistent atrial fibrillation patient population existed, so the performance goal of 16 percent was established based on a literature review evaluating ablation procedures in paroxysmal atrial fibrillation ablation patients. These specific safety findings were not unexpected since persistent or long-standing persistent atrial fibrillation patients undergoing ablation have a higher risk of adverse events due to the advanced state of the disease and the complexity of the procedure.