Cardiovascular Drug Trial Discontinued

In mid-January, a combined Data Safety and Monitoring Board (DSMB) halted one of two Phase III trials of Merck's investigational anti-clotting drug vorapaxar because of increased risk of bleeding—specifically intracranial hemorrhage—in subjects with a history of stroke.

The TRACER study was being conducted by Duke Clinical Research Institute. It was fully enrolled in June 2010 and included 13,000 subjects with non-ST-segment-elevation acute coronary syndrome. TRA-2P, or TIMI 50 as the trial was also known, was fully enrolled in November 2009 and included 26,500 subjects who had previously experienced a heart attack. The study was being conducted by Brigham and Women's Hospital.

The DSMB instructed TRACER investigators to discontinue the study drug in subjects and begin close-out activities. For TRA-2P, investigators were told to discontinue the study drug in those who experienced a stroke prior to entering or during the course of the study. They could continue the study drug in those who entered the trial with a history of a previous heart attack or peripheral arterial disease, an estimated 75% of the subjects.

The www.clinicaltrials.gov identifier for the TRACER trial is NCT00527943, and NCT00526474 for TRA-2P. Peter Kim, PhD, President of Merck Research Laboratories, emphasized in a conference call that the goal of vorapaxar was to find "an antiplatelet agent that we could add on top of standard of care." Vorapaxar is one of the company's key programs in Phase III, and it had anticipated filing for approval this year. While financials were not discussed, at an estimated cost of $26,000 per subject in Phase III trials, this represents a $338 million hit to the company's bottom line.