A study of an experimental blood thinner from Merck & Co. (MRK) showed that while the drug helped thwart heart attacks it raised the risk of brain bleeding, a side effect that could stymie its approval.

The three-year study of 26,449 patients who had heart attack, stroke or leg artery disease, found those who got Merck’s vorapaxar along with standard therapy were 13 percent less likely to have another heart attack or die from cardiovascular causes than those on standard treatment. More patients on the drug also had serious bleeding, according to data reported today at the American College of Cardiology meeting in Chicago.

The findings are unlikely to be good enough to get U.S. marketing approval, said Steven Nissen, a cardiologist at the Cleveland Clinic who wasn’t involved in the study. New studies are needed to prove vorapaxar can be used in some patients without excess bleeding, he said.

“The results are disappointing,” said Nissen. “The bottom line is it is extremely difficult to make the case that the benefits exceed the risks here.”

In January 2011, Merck narrowed the scope of the trial to stop testing the drug in stroke patients and halted another vorapaxar trial entirely after doctors monitoring the results found an increased risk of brain hemorrhage in those patients. Merck, based in Whitehouse Station, New Jersey, later took a $1.7 billion charge to write down the value of the drug.

Efficacy Goal
Merck Vice President Francis Plat, in an interview at the meeting, called the company-funded vorapaxar study “positive” because it achieved its efficacy goal of preventing heart attacks and heart-related deaths. He said the company is discussing with top cardiologists what role the new medicine might play and which patient groups are likely to benefit.
Until those talks are done, “it is difficult for us to anticipate any strategy in terms of filing” for regulatory approval, he said.

David Morrow, a cardiologist at Brigham & Women’s Hospital in Boston who led the study, said that the drug’s benefit was compelling in the subset of 17,779 patients who had previous heart attacks. In that group, vorapaxar reduced the risk of heart attacks, strokes and cardiovascular death by 20 percent.

“There is potential for benefit in that group that clearly outweighs the risk of bleeding,” Morrow said in a telephone interview.

Blood Thinner Challenge

The findings illustrate how difficult it is for drugmakers to come up with new blood thinners that work well on top of standard therapy without excessive bleeding, Nissen said in a phone interview. Heart patients typically take aspirin and also often take the blood thinner Plavix from Sanofi and Bristol- Myers Squibb Co. to reduce future risk.

“Anything where there is significantly more bleeding is a difficult sell for doctors,” said Kim Vukhac, an analyst at Credit Agricole Securities in New York, in a telephone interview before the data was released. Investor “expectations are low” for vorapaxar, he said.

The Merck study added vorapaxar to standard therapy to see whether the drug safely provided greater protection from heart attacks, strokes, and cardiovascular deaths. The study met this primary goal.

The research showed that 148 fewer patients on vorapaxar got heart attacks, strokes or died of cardiovascular disease, as compared with those on placebo with the standard therapy, according to results being published in the New England Journal of Medicine in conjunction with the meeting.

The study also found 171 more patients on vorapaxar experienced moderate to severe bleeding. Also, the rate of brain bleeding doubled in the vorapaxar group. The brain bleeding risk was highest in patients who had a previous stroke, according to the results.

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To contact the reporter on this story: Robert Langreth in New York at .(JavaScript must be enabled to view this email address).

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By Robert Langreth