Merck ( MRK ) recently announced top-line data on its anti-clotting candidate, vorapaxar, from the TRA-2P (Thrombin Receptor Antagonist in Secondary Prevention of atherothrombotic ischemic events) study. Although vorapaxar achieved its primary endpoint, bleeding risks were, once again, high.

Results showed that vorapaxar, when added to standard of care, significantly reduced the risk of cardiovascular death, heart attack (myocardial infarction), stroke or urgent coronary revascularization compared to the standard of care.

However, a significant increase in bleeding, including intracranial hemorrhage ( ICH ) or bleeding within the brain, was observed in the vorapaxar arm. Merck noted that the risk of ICH was lower in patients who had not suffered a stroke previously.

TRA-2P was a prevention study conducted in patients who have experienced a heart attack or ischemic stoke or who have documented peripheral artery disease (PAD). Full results from this study will be presented at the American College of Cardiology Scientific Sessions to be held in March.

Vorapaxar has already been in the news due to its higher bleeding risk. Merck had presented disappointing results on the candidate from another study at the American Heart Association in 2011. Results from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study showed that vorapaxar failed to meet its primary endpoint.

Besides failing to achieve its primary endpoint, a higher rate of bleeding was observed in the vorapaxar treatment arm compared to the standard of care. There was also a three-fold increase in intracranial hemorrhage.

Vorapaxar is being developed by Merck for the prevention of thrombosis and the reduction of cardiovascular events. Now that results from the TRA-2P study are available, Merck intends to review data from both studies before deciding on the regulatory path for the candidate.

We note that vorapaxar did not feature in Merck's planned regulatory filings for 2012 and 2013 when the company announced fourth quarter results earlier this month. The five candidates that will be filed for regulatory approval include Bridion (a neuromuscular reversal agent), V503 (an investigational vaccine to help protect against certain HPV associated cancers), odanacatib (once-weekly oral treatment of osteoporosis), Tredaptive (atherosclerosis) and suvorexant (insomnia).

Neutral on Merck

We currently have a Neutral recommendation on Merck, which carries a Zacks #3 Rank (short-term ). With vorapaxar, Merck is looking to carve a position in a market which is dominated by players like Bristol-Myers Squibb Co.'s ( BMY ) Plavix, Eli Lily & Co.'s ( LLY ) Effient and AstraZeneca plc's ( AZN ) Brilinta among others. However, the increase in bleeding associated with vorapaxar could make it challenging for the candidate to take share once approved.