Palo Alto, CA - Two weeks in advance of the American College of Cardiology (ACC) 2007 Scientific Sessions, negative results of the MERLIN TIMI-36 trial testing ranolazine (Ranexa, CV Therapeutics) in acute coronary syndrome (ACS) patients—scheduled as a late breaker at the meeting—have been released by the study sponsor. An analysis of unblinded data from the trial indicated that it would not meet its primary efficacy composite end point of time to first occurrence of cardiovascular death, MI, and/or recurrent ischemia, a press release states.

The study, sponsored by CV Therapeutics, compared long-term treatment with extended-release ranolazine with placebo, on top of standard therapy, for acute and long-term treatment of patients with non-ST-elevation ACS.

The safety end point, however, showed no adverse trends in death or arrhythmia—a finding that the company hopes will help the drug earn FDA support for expansion of its current labeling. As previously reported by heartwire, the FDA, concerned that the drug, by prolonging QT interval, might lead to arrhythmias, approved ranolazine in January 2006 as a second-line treatment for chronic angina only in patients who do not respond to other antianginal agents.

According to a company spokesperson, the FDA had asked the company to provide long-term safety data for the drug to prove it could be used as a first-line treatment for chronic angina. So while the MERLIN TIMI-36 results will not lead to a new indication for ranolazine in ACS patients, the two-year safety data showing no increased death or arrhythmia should satisfy the FDA's request.

Early announcement of the negative results smacks of leaking bad news early—"late-breaking" clinical trial results are usually strictly embargoed until the hour they are presented during the scientific sessions. In this case, however, the ACC has confirmed that the college reviewed and approved the CV Therapeutics press release before it was issued.

"SEC regulations require companies to disclose information that may have major impact on their stock price," ACC president Dr Steven Nissen (Cleveland Clinic, OH) explained to heartwire. "This usually occurs with small companies, such as CV Therapeutics. We agreed to allow extremely limited information—essentially revealing only that the study failed to meet its prespecified end point."

The company, not surprisingly, does not view the MERLIN TIMI-36 trial entirely as bad news, pointing out that "bad news" would have been a failed primary end point and safety issues with the drug. Company spokesperson John Bluth pointed out to heartwire that some physicians may have been reluctant to use ranolazine out of fears of torsades de pointes caused by the QT-interval prolongation. Those fears have not materialized, Bluth said.