Bayer/J&J anti-clot drug cuts death in heart study

Low doses of Bayer AG and Johnson & Johnson’s Xarelto blood clot preventer cut the risk of death by more than 30 percent when used on top of standard blood thinners in patients with acute coronary syndrome, according to data from a study released on Sunday.

The companies had previously revealed that Xarelto met the study’s main goal of significantly reducing the combined risk of death, stroke or heart attack when used on top of Plavix and aspirin compared with those standard medicines alone.

In the Atlas study of 15,526 patients suffering from acute coronary syndrome (ACS), those who received Xarelto, known chemically as rivaroxaban, had a 16 percent combined reduced risk of death, stroke or heart attack, which researchers considered to be highly statistically significant.

For the lowest of the two tested Xarelto doses—2.5 milligrams twice a day—the risk of cardiovascular death was cut by 34 percent and all causes of death by 32 percent, according to data presented at the American Heart Association scientific meeting in Orlando.

“The real kicker was mortality. It was just a highly significant response,” said Dr Eugene Braunwald, the study’s chairman from Brigham and Women’s Hospital in Boston.

Sanford Bernstein analyst Tim Anderson said demonstrating a meaningful overall mortality benefit could translate into an additional $2 billion or $3 billion opportunity for the Bayer and J&J medicine.

As previously reported, Xarelto led to a significant increase in bleeding when used on top Plavix and aspirin, including intracranial hemorrhage. But there was no increase in fatal bleeding and researchers felt the increased bleeding risk was offset by the mortality reduction.

“I’d rather have a major bleed and walk out of the hospital than not have a bleed and be wheeled to the morgue, so all cause mortality is the most important thing,” Braunwald said.

There was also another benefit seen with the Xarelto group in patients who had previously received a stent in an artery clearing procedure—about 60 percent of study participants.

Stent thrombosis, or reclogging of the treated artery, was reduced by 31 percent in patients taking the Bayer and J&J pill.

“This is a real difference on top of dual antiplatelet therapy,” Braunwald said.

‘EXCEEDED OUR EXPECTATIONS’

Xarelto, which inhibits a protein called factor Xa involved in the blood clotting process, is one of three new drugs vying for position in the multibillion-dollar anti-clot market along with axpixaban from Pfizer Inc and Bristol-Myers Squibb and Pradaxa from Boehringer Ingelheim. Apixaban previously failed in a similar study of ACS patients.

Earlier this month, Xarelto won U.S. approval for preventing strokes in patients with a dangerously irregular heartbeat called atrial fibrillation, considered by far the largest and most lucrative use for the new generation of blood thinners.

Researchers and company officials believe the data presented on Sunday are likely to be seen as strong enough for Xarelto to gain an additional approval to treat ACS—an umbrella term that refers to patients’ who have heart attacks or chest pain usually caused by a blocked coronary artery.

“The results exceeded our expectations,” said Peter DiBattiste, J&J’s head of cardiovascular and metabolism, adding that the companies plan to apply for U.S. and European approval for use in ACS patients by the end of the year.

An editorial in the New England Journal of Medicine accompanying the data, while generally positive, somewhat tempered the enthusiasm, noting that only 9 percent of study subjects were at least 75 years old and more than 75 percent had normal kidney function.

“The results may not be applicable to higher-risk patients with an acute coronary syndrome who are commonly treated in routine practice,” it said.

About a million patients in the United States are hospitalized each year after having an ACS episode, usually a heart attack, researchers said.

The majority of the patients in the study were already on Plavix and aspirin—the current standard of care—although about 7 percent were taking only aspirin. Study subjects were then given a placebo, 5 milligrams of Xarelto twice a day or 2.5 mg of Xarelto twice a day.

“When we compared 2.5 with 5, the 2.5 was superior on efficacy and superior to 5 mg on safety,” Braunwald said.

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By Bill Berkrot and Lewis Krauskopf

ORLANDO, Florida