In the large TRA-2P study of more than 26,000 patients with MI, ischemic stroke, or documented peripheral vascular disease, the novel antiplatelet agent vorapaxar significantly reduced the primary endpoint of CV death, MI, stroke or urgent coronary revascularization. But vorapaxar treatment resulted in a significant increase in bleeding, including intracranial hemorrhage.
The fate of vorapaxar now appears to be uncertain, as the company said it will review data from the drug’s two large clinical trials with the investigators of the trials and external experts to inform the company’s next steps.
The full results of the TRA-2P (Thrombin Receptor Antagonist in Secondary Prevention of atherothrombotic ischemic events) trial are scheduled to be presented in March at the American College of Cardiology. Merck today released the top-line results in a press release.
TRACER, the large ACS trial with vorapaxar, was terminated early last year due to similar safety concerns. As reported here last year, at the same time TRACER was stopped the TRA-2P trial was modified. TRA-2P investigator Eugene Braunwald said that vorapaxar would be discontinued in patients who experienced a stroke prior to entry or during the trial because of an increase in intracranial hemorrhage in these patients.
On his blog on Forbes Matt Herper provides some additional perspective on this story.
Here is the press release from Merck:
Merck Announces Top-Line Results of TRA-2P Study of Vorapaxar
|Company Will Review Data FromTRA-2P and TRACER With External Experts to Inform Next Steps|
|WHITEHOUSE STATION, N.J., Feb. 7, 2012 – Merck (NYSE:MRK), known outside the United States and Canada as MSD, today announced the top-line results of the TRA-2P (ThrombinReceptor Antagonist in Secondary Prevention of atherothrombotic ischemic events) study of vorapaxar. Merck is developing vorapaxar, an investigational oral Protease Activated Receptor 1 (PAR-1) thrombin receptor antagonist, for the prevention of thrombosis, or clot formation, and the reduction of cardiovascular events.TRA-2P showed that the addition of vorapaxar to standard of care significantly reduced the risk of the protocol-specified primary endpoint of the composite of cardiovascular death (CVD), heart attack (myocardial infarction, or MI), stroke or urgent coronary revascularization compared to standard of care. There was a significant increase in bleeding, including intracranial hemorrhage (ICH), among patients taking vorapaxar in addition to standard of care, although there was a lower risk of ICH in patients without a history of stroke.The full results of TRA-2P will be presented at the American College of Cardiology Scientific Sessions in March.
“In developing vorapaxar, Merck and our scientific collaborators set a very high bar – would the addition of vorapaxar to standard of care provide incremental benefit in preventing clots?” said Peter S. Kim, president, Merck Research Laboratories. “We are pleased that TRA-2P met its primary endpoint, and we look forward to discussing the results with the scientific community.”
Merck will review the data from both TRA2-P and TRACER with the investigators and other outside experts to help better understand the profile of this investigational medicine in specific patient populations and to determine next steps, including potential regulatory filings.
Vorapaxar has been evaluated in two major clinical outcomes studies: TRA-2P TIMI 50 (Clinicaltrials.gov identifier: NCT00526474 ) was led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group of Brigham and Women’s Hospital. TRA-2P was a secondary prevention study in 26,449 patients with a heart attack, an ischemic stroke, or documented peripheral vascular disease. TRACER (Thrombin Receptor Antagonist for Clinical EventReduction in Acute Coronary Syndrome), (Clinicaltrials.gov identifier: NCT00527943) was an acute care, hospital-based study of approximately 12,944 patients with non-ST-segment-elevation acute coronary syndrome. The study was led by the Duke Clinical Research Institute, and results were presented in 2011 at the American Heart Association Scientific Sessions and published in the January 5, 2012 issue of The New England Journal of Medicine (Vol. 366, No. 1). The news release can be found at http://www.merck.com/newsroom/news-release-archive/research-and-development/2011_1113.html.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the United States and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
|# # #|