Johnson & Johnson and Bayer AG (BAYN)’s blood-thinner Xarelto cut by 16 percent the risk of a subsequent heart attack, stroke or death from heart disease in patients who recently suffered a cardiac event, according to a study.
The data makes Xarelto the first in a new class of blood thinning medicines to show effectiveness for acute coronary syndromes, or ACS, when used in addition to standard treatment. The lowest dose, given twice daily, slashed deaths by one-third.
Xarelto was approved Nov. 17 in the U.S. to prevent strokes in people with atrial fibrillation, an irregular heartbeat that affects more than 2 million Americans. The data reported today at the American Heart Association meeting in Orlando, Florida, may create a new use in 1.2 million patients hospitalized yearly with ACS, which includes heart attack and severe chest pain. It’s a $1.4 billion market, said Tim Anderson, an analyst with Sanford C. Bernstein & Co. in San Francisco.
“The mortality difference was pretty impressive,” said Deepak Bhatt, chief of cardiology at the VA Boston Healthcare System and director of the interventional cardiovascular program at Brigham and Women’s Hospital in Boston, in an interview. “It’s hard in cardiovascular medicine to find trials with a mortality benefit.”
Still, doctors discussing the results at a press conference today emphasized that the drug has a downside of higher rates of major bleeding episodes, including brain hemmorhage.
Xarelto competes with Pradaxa from Boehringer Ingelheim GmbH of Ingelheim, Germany in the atrial fibrillation market. Another rival drug, Eliquis from Pfizer Inc. (PFE) and Bristol-Myers Squibb Co. (BMY), both based in New York, presented positive trial results in atrial fibrillation at a conference in August.
All three drugs are attempting to replace warfarin, a more than 50-year-old medicine that is a form of rat poison. The Xarelto study was funded by New Brunswick, New Jersey-based Johnson & Johnson, which owns U.S. rights, and Leverkusen, Germany-based Bayer, which sells the treatment in Europe.
Until today’s results, it wasn’t clear that the new class of drugs would also work in acute coronary patients, who are treated with aspirin and the blood thinner Plavix from Paris- based Sanofi and Bristol. Pfizer’s Eliquis flopped in a trial of ACS patients a year ago, failing to prevent heart attacks and cardiac deaths while causing significantly more major bleeding.
A study of Merck & Co.’s vorapaxar, also presented at the meeting, boosted rates of severe bleeding in the brain more than three-fold and failed to reduce deaths, heart attacks, strokes and other complications in high-risk heart patients.
“We are really excited about this result,” said Peter DiBattiste, global therapeutic area head of cardiovascular disease at Johnson & Johnson (JNJ), in an interview. “This is a significant advance here over the standard of care.”
In the new trial, doctors used very low doses of Xarelto given twice daily and excluded patients with prior strokes to minimize bleeding. Still, patients on Xarelto had a more than 3- fold increase in major bleeding episodes. The rate of fatal bleeding did not increase significantly, according to results being published in the New England Journal of Medicine in conjunction with the conference.
Bayer has estimated that sales of Xarelto will top $2.8 billion annually. The companies plan to file for FDA approval for the acute coronary use by the end of the year. They will ask the FDA for a priority review, though it hasn’t decided whether it will request approval of both doses or just the lower dose, DiBattiste said.
Improvement for ACS
Doctors said the drug could improve care for acute coronary syndrome patients.
“Although we have made a lot of progress in caring for these patients in the hospital, once they leave they still have significant risks and high death rates,” said Eugene Braunwald, professor at Harvard Medical School and study author at Brigham and Women’s Hospital in Boston. “The statistical benefit for the very low dose is powerful.”
Patients in the new Xarelto trial were given 2.5 milligrams of Xarelto, 5 milligrams of Xarelto or a placebo twice a day. Everyone also took aspirin and the vast majority used Plavix.
Doctors followed the patients for a median of 13 months. Heart attacks, stroke and death from cardiovascular disease occurred in 8.9 percent of patients given Xarelto, compared with 10.7 percent of those on placebo.
Death from cardiovascular disease was reduced by 34 percent in the low-dose arm compared with placebo, while deaths from any cause were down 32 percent. The higher 5 milligram dose didn’t reduce mortality rates, for reasons that aren’t totally clear.
Preventing One Death
Doctors would need to treat 56 patients for two years with low-dose Xarelto to prevent one death, said Michael Gibson, senior author on the study and chief of clinical research at Beth Israel Deaconess Medical Center’s Cardiovascular Institute, at a press conference at the heart meeting.
Still, the increased bleeding seen with Xarelto is something doctors and patients need to keep in mind when determining treatment, Braunwald said.
“You have to take serious bleeding seriously,” he said in a telephone interview. “I would rather have a patient have a serious bleed who walks out of the hospital than someone who dies without a bleed.”
Major bleeding episodes occurred in 2.4 percent of patients on the high dose of Xarelto and 1.8 percent of those on the low dose, versus 0.6 percent of those on placebo.
“The very low dose was better on efficacy by a lot because it showed a reduction in mortality, a smaller increase in bleeding and it wasn’t associated with fatal bleeding,” Braunwald said.
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