Merck & Co., Inc. today said that preliminary results for the pivotal Phase III study of rolofylline (MK-7418), the company’s investigational medicine for the treatment of acute heart failure, show that rolofylline did not meet the primary or secondary efficacy endpoints. While Merck will continue to analyze the data with outside experts, the company will not file applications for regulatory approval this year. The results from this study will be presented at a medical meeting later this year. “Advances to help patients with acute heart failure, a disease that is the leading cause of hospitalization for patients over age 65 and that is associated with a high rate of mortality, have long been elusive,” said Dan Bloomfield, M.D., executive director, cardiovascular research, Merck Research Laboratories. “These results are disappointing because we had been hopeful that blocking the adenosine A1 receptor with rolofylline would prove to be a useful new approach for these patients. “Merck remains committed to discovering and developing novel treatments for heart failure and for cardiovascular disease, which claim more than 17 million lives worldwide each year and remain the leading cause of death and a leading cause of disability,” Dr. Bloomfield said. The primary hypothesis of the 2,033-patient pivotal Phase III study, PROTECT, was that rolofylline 30 mg would improve symptoms of acute heart failure compared to placebo. The secondary endpoints were that rolofylline 30 mg would reduce the risk of death or cardiovascular or renal re-hospitalization 60 days after treatment, and that rolofylline 30 mg would reduce the incidence of persistent kidney impairment. Details on the design of PROTECT are available at www.clinicaltrials.gov, identifiers NCT00328692 and NCT00354458. Rolofylline was acquired by Merck through NovaCardia, which Merck purchased in 2007. Results from the PROTECT pilot study, presented at previous medical meetings and published in 2008, had showed an overall trend toward efficacy (more patients with improved shortness of breath, fewer patients with worsening renal function and/or worsening heart failure). Merck’s late-stage pipeline of investigational medicines for cardiovascular disease includes MK-524A (approved in some markets outside the U.S.), MK-524B, ezetimibe/atorvastatin, and anacetrapib (MK-0859) for atherosclerosis, and vernakalant for atrial fibrillation.
