Merck & Co has confirmed that an excessive bleeding problem was the reason why stroke patients have been removed from studies of its investigational blood clotter vorapaxar.
Last week, the US drugs major announced changes to two trials - the 26,5000-patient TRA-2P study in people with prior heart attack, stroke and peripheral artery disease, and TRACER, a 13,000-patient study for acute coronary syndrome. It said that TRACER was being stopped, while in TRA-2P, vorapaxar will be continued in patients who had experienced a previous heart attack or peripheral arterial disease (75% of the patients enrolled in the study), but immediately discontinued in patients who experienced a stroke.
Now Merck says it has been provided with additional information about the recommendations of the data and safety monitoring board regarding TRA-2P. Eugene Braunwald, chairman of the TRA-2P trial, told investigators that "the DSMB has communicated to us that based on all of the data (safety and efficacy) available to them from both trials, they recommend that subjects with a history of stroke not receive vorapaxar".
He added that the board has observed "an increase in intracranial haemorrhage in patients with a history of stroke that is not outweighed by their considerations of potential benefit." However, Dr Braunwald stressed that the DSMB "recommended to us that it is important that the trial continue to completion in the more than 20,000 subjects who qualified for the trial with myocardial infarction or peripheral arterial disease who have not had a stroke". He concluded that "on the basis of their recommendation, we and Merck remain committed to completing this important scientific investigation".
Vorapaxar, a first-in-class thrombin receptor antagonist vorapaxar, was touted as one of the most promising compounds in the pipeline of Schering-Plough, acquired by Merck for $41 billion in 2009. However news of the study changes led to a share price decline that wiped almost $8 billion from the stock.