Patients in novel clinical trial will have cardiac rhythms continuously monitored with implanted Medtronic devices.
ARCA biopharma, Inc. announced that it has entered into an agreement with Medtronic, Inc. to collaborate on ARCA’s proposed clinical trial, known as GENETIC-AF, of its lead developmental drug Gencaro (bucindolol hydrochloride).
GENETIC-AF is planned as a Phase 2b/3 clinical trial comparing Gencaro to metoprolol CR/XL for prevention of atrial fibrillation (“AF”) in patients with heart failure and reduced left ventricular ejection fraction ("HFREF"). ARCA plans to enroll only patients with the genetic variant of the beta-1 cardiac receptor which the Company believes responds most favorably to Gencaro. GENETIC-AF has an adaptive design, under which the Company plans to initiate it as a Phase 2b study in approximately 200 patients and then, depending on the results of an interim analysis, expand the trial to a Phase 3 study by enrolling an estimated additional 420 patients.
Under the collaboration, ARCA plans, with the support of Medtronic, to conduct a substudy that will include continuous monitoring of the cardiac rhythms of all 200 patients enrolled during the Phase 2b portion of GENETIC-AF. Each patient will have heart rhythm monitoring via a Medtronic device, either a previously implanted cardiac resynchronization or defibrillation device, or a previously or newly inserted Reveal® loop recorder. The collaboration substudy will measure AF burden, defined as a patient’s actual time in AF regardless of symptoms. In determining the presence of an efficacy signal in the Phase 2b portion of the trial, AF burden will be evaluated along with time to mortality or recurrent AF, which will also be the Phase 3 primary endpoint.
ARCA believes that the AF burden endpoint will help provide an accurate and comprehensive assessment of each patient’s AF episodes, and will be useful in evaluating the relative efficacies of Gencaro and metoprolol CR/XL. Under the collaboration, Medtronic will support the implantation and use of the Medtronic monitoring devices, and will manage the AF burden data collection and analysis. If GENETIC-AF proceeds to Phase 3, the parties will seek to enroll at least 100 additional patients in the AF burden substudy.
Dr. Michael Bristow, MD, PhD, President and Chief Executive Officer of ARCA, said, “We are excited about our collaboration with Medtronic on GENETIC-AF. We believe that the use of implanted, continuous monitoring devices that allow for the more precise measurement of atrial fibrillation represents the next generation of diagnosis and treatment options for patients at risk for this disease. The GENETIC-AF trial has the potential to result in an approvable new therapy that is safe and effective for HFREF patients at high risk for atrial fibrillation.”
AF is considered an epidemic cardiovascular disease with an estimated prevalence of at least 2.7 million Americans in 2010. The approved therapies for the treatment or prevention of AF have certain disadvantages in HFREF patients, such as toxic or cardiovascular adverse effects, and most of the approved drugs for AF are contra-indicated or have warnings in their prescribing information for such patients. ARCA believes there is an unmet medical need for new AF treatments that have fewer side effects than currently available therapies and are more effective, particularly in HFREF patients.