Merck (known as MSD outside the United States and Canada) provided the following statement on the changes to the clinical studies for vorapaxar, one of the Company's investigational cardiovascular medicines, following an announcement from the two academic centers leading the studies of vorapaxar.

Merck is studying vorapaxar in two major clinical endpoint trials to evaluate the investigational medicine for the prevention of cardiac events: TRACER, a study in patients with acute coronary syndrome, and TRA-2P (also known as TIMI 50), a study in patients with prior heart attack, stroke and peripheral artery disease. Both studies are event-driven trials in which patients were planned to be followed for a minimum of one year, and both had completed enrollment.

The combined Data and Safety Monitoring Board for the two studies has reviewed the available safety and efficacy data, and made recommendations for study changes to the chairpersons. The study chairpersons have agreed to implement these changes, and communicated the following information to study investigators:

- In the TRACER study, patients will discontinue study drug and investigators are to begin now to close out the study in a timely and orderly fashion.

- In the TRA-2P study, study drug will be continued in patients who had experienced a previous heart attack or peripheral arterial disease (approximately 75 percent of the patients enrolled in the study), and will be immediately discontinued in patients who experienced a stroke prior to entry into the study or during the course of the study.

Merck plans to update its projections for regulatory filings for vorapaxar once the Company has received the efficacy and safety data from TRACER and can determine an updated completion date for TRA-2P.

TRACER has accumulated the pre-defined number of primary and major secondary endpoints, although not all patients will continue to receive study drug through the pre-specified one-year follow up. Merck continues to expect that the efficacy and safety data from TRACER will become available later this year and will be submitted for presentation at appropriate medical meetings.

"Cardiovascular disease remains the world's leading killer, and despite all of the advances that have been made in the field, millions of patients remain at risk for major cardiovascular events," said Peter S. Kim, Ph.D., president, Merck Research Laboratories. "We remain committed to conducting large clinical trials such as TRACER and TRA-2P that are so critical to understanding new cardiovascular medicines and to advancing the standard of care for patients with heart disease. We thank the investigators and the patients involved in these two studies for their continued efforts to understand the potential role of vorapaxar in the treatment of cardiovascular disease."

Additional Background

Vorapaxar is a selective PAR-1 (Protease Activated Receptor 1) Thrombin Receptor Antagonist designed to diminish thrombosis (clot formation).

TRACER is an acute care (hospital-based) study of approximately 13,000 patients with non-ST-segment-elevation acute coronary syndrome. In TRACER, vorapaxar was administered starting with a 40 mg loading dose, followed by a 2.5 mg daily dose. The study completed enrollment in June 2010.

The primary endpoint of TRACER is the first occurrence of any component of the composite of cardiovascular death, heart attack, stroke, recurrent ischemia with re-hospitalization, and urgent coronary revascularization, compared to active control. (Clinicaltrials identifier: NCT00527943; A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of SCH 530348 in Addition to Standard of Care in Subjects With Acute Coronary Syndrome: Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome.)

TRA-2P, or TIMI 50, is a chronic care, secondary prevention study of approximately 26,500 patients who have experienced a heart attack, an ischemic stroke, or have documented peripheral vascular disease. In TRA-2P, vorapaxar is administered at a 2.5 mg daily dose. The study completed enrollment in November 2009.

The primary endpoint of TRA-2P is the first occurrence of any component of the composite of cardiovascular death, MI, stroke, and urgent coronary revascularization compared to placebo. (Clinicaltrials identifier: NCT00526474; A Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients with Atherosclerosis.)

Source:
Merck