A study showing Johnson & Johnson and Bayer AG’s blood-thinner Xarelto succeeded where rival drugs failed in reducing deaths following a heart attack promises to give the companies entry to a $1 billion-plus market.
Based on data reported Sunday at the American Heart Association meeting, J&J, of Whitehouse Station, N.J., and its German partner, Bayer, said they plan by year’s end to seek Xarelto’s approval for treating acute coronary syndrome, or ACS, a designation that includes heart attacks and chest pain and results in 1.2 million hospitalizations a year.
“This is going to be such a competitive field as multiple drugs jockey for position,” said Robert Harrington, director of Duke University’s Clinical Research Institute in Durham, N.C. “There is going to be some time before people figure out” how to use the new treatments, he said.
If cleared for ACS, Xarelto would enter a market that includes Brilinta from London-based AstraZeneca Plc and Effient from Indianapolis-based Eli Lilly & Co. These drugs are used instead of the standard treatment, Plavix, a drug made by New York-based Bristol-Myers Squibb Co. and Paris-based Sanofi. Xarelto would likely be used in concert with Plavix.
Lilly sold about $128 million of Effient in the first half of the year and expects the drug to be a significant performer.
Even with good care, patients hospitalized for ACS remain at high risk of having a subsequent heart attack or stroke.
While doctors have been attempting to come up with better blood thinners for heart patients for years, it has been tricky to do this without causing too much bleeding.
In its new study of 15,526 patients, J&J and Bayer narrowly succeeded in finding a dose that was effective at preventing heart attacks and heart deaths without unacceptable bleeding, according to doctors at the annual heart meeting, held this year in Orlando, Fla.
Overall, the drug reduced heart attacks, strokes, and cardiovascular deaths by 16 percent, the researchers reported. The reduction in deaths was only seen in the lower of two doses tested, they said.
“Xarelto appears to have hit the “sweet spot” for efficacy with an acceptable safety profile,” wrote Seamus Fernandez, an analyst at Leerink Swann, in a research note. He predicted the low dose will be approved by the U.S. Food and Drug Administration for ACS and “can be a meaningful competitor in an increasingly crowded space that has been relatively slow to develop commercially.”
The market for ACS drugs will likely exceed $1 billion, he said.
“The mortality difference was pretty impressive,” said Deepak Bhatt, director of the interventional cardiovascular program at Brigham and Women’s Hospital in Boston. “It’s hard in cardiovascular medicine to find trials with a mortality benefit.”
Still, doctors discussing the results at the conference emphasized that that drug has a downside of higher rates of major bleeding episodes, including bleeding in the brain.
Drugs already marketed for ACS, including Brilinta, Effient and Plavix, block cell fragments in the blood called platelets from sticking together. Xarelto, by contrast, blocks a second process involved in clotting, an enzyme involved in producing fibers that help the blood coagulate.
Pradaxa from German drugmaker Boehringer Ingelheim GmbH and Eliquis from New York-based Pfizer Inc. and Bristol-Myers Squibb Co. are from the same family of medicines. Until Sunday’s results, it wasn’t clear this class would be a competitor in ACS patients. Eliquis a year ago failed to prevent heart attacks and cardiac deaths in a study while causing more major bleeding.
All three treatments are attempting to replace standard use of warfarin, a more than 50-year-old medicine that is a form of rat poison.
The Xarelto study was funded by New Brunswick, N.J.- based Johnson & Johnson, which owns U.S. rights, and Leverkusen, Germany-based Bayer, which sells the treatment in Europe.
“We are really excited about this result,” said Peter DiBattiste, global therapeutic area head of cardiovascular disease at Johnson & Johnson. “This is a significant advance here over the standard of care.”
One reason why the Xarelto study may have worked is that it used a low dose to minimize bleeding, only one-half to one-quarter of the Xarelto dose used to treat atrial fibrillation, said Paul W. Armstrong a cardiologist at the University of Alberta in Edmonton. He estimated that one-fourth to one-third of ACS patients could benefit from the Xarelto triple drug cocktail.
The U.S. Food and Drug Administration will have to review the data, particularly the risk of bleeding, doctors at the conference said. Some were concerned that bleeding rates could turn out to be higher outside the carefully controlled conditions of a big clinical trial.
“I worry that if you are going to release a drug like this into the real world, you are going to deal with bleeding incidents and the payoff may not be there,” said Jack Ansell, a hematologist and chairman of the department of medicine at Lenox Hill Hospital in New York. “I don’t think this is ready for prime time.”
Doctors involved with the study said the drug can improve care of heart patients when used carefully.
“The statistical benefit for the very low dose is powerful,” said Eugene Braunwald, professor at Harvard Medical School and study author at Brigham and Women’s Hospital in Boston. “I would rather have a patient have a serious bleed who walks out of the hospital than someone who dies without a bleed.”