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New Blood Thinner Matches Warfarin

AUGUST 31, 2009

By RON WINSLOW

A blood thinner being developed by Boehringer Ingleheim GmbH proved to be at least as effective as the workhorse heart drug warfarin in a trial that researchers said could help usher in a new era for preventing stroke in millions of patients with a heart-rhythm disorder called atrial fibrillation.

In an 18,113-patient trial, a high dose of the drug, called dabigatran, reduced the rate of stroke by 34% compared to warfarin, with a comparable rate of major bleeding episodes. With a lower dose, the rate of stroke was similar while the rate of bleeding was similar.

It was first time in a major study that an oral treatment has at least matched warfarin -- a drug that has been on the market for more than a half century -- on both effectiveness and safety, researchers said. An AstraZeneca PLC drug called ximelagatran came close, but failed when it proved toxic to the liver.

"The world has been waiting for more than two decades for a replacement for warfarin and it looks like we have one such medication," said Christopher Cannon, a cardiologist at Brigham and Women's Hospital, Boston, who wasn't involved in the study.

Warfarin, marketed by Bristol-Myers Squibb Co. as Coumadin and available in generic versions, is an anticoagulant that prevents formation of blood clots in the heart of patients with atrial fibrillation -- where they can spread to the brain or lungs with calamitous effects.

It is tricky, however, to maintain the right balance of Warfarin in patients: If the blood gets too thin, there is the potential for causing bleeding in the brain and other problems; if it is too thick, it can lead to clots. Moreover, warfarin reacts with dozens of other drugs and with food such as green vegetables. A patient's genetics can also blunt its effectiveness.

As result, "you have to monitor patients on warfarin at least every month in order to optimize care," said Michael Ezekowitz, a cardiologist at Lankenau Institute for Medical Research, Wynnewood, Pa.. He was a co-leader of the dabigatran study, which was sponsored by Boehringer.

An estimated 3 million Americans have atrial fibrillation, which afflicts about one in 10 people over age 70. Yet because of warfarin's challenges to both doctors and patients, only about half of patients who should be treated are on the medicine, according to some estimates.

In addition to Boehringer Ingelheim's dabigatran, which is on the market in Europe for stroke prevention after hip and knee surgery, at least three other compounds are in or moving into late stages of development as alternatives to warfarin. Johnson & Johnson and Bayer AG's Xarelto is also available in the market in Europe for the surgery indications. Bristol-Myers and Pfizer Inc. are co-developing apixaban. Merck & Co. recently joined forces with Portola Inc. to develop that startup's drug betrixaban.

The dabigatran data were presented Sunday at a meeting of the European Society of Cardiology in Barcelona. They were also published in the New England Journal of Medicine.

In the group given 110 milligrams of dabigatran, the low dose, the rate of stroke and other events where clots were dislodged in the heart and carried to other parts of the body was 1.53% per year, compared with 1.69% for those taking warfarin and 1.11% in the higher-dose, 150-milligram group. Major bleeding episodes occurred in 3.36% of warfarin patients per year, compared with 2.71% for patients on 110 milligrams of dabigatran and 3.11% on 150 milligrams.

If all goes well with Boehringer Ingleheim's approval applications, the drug could win U.S. and European regulatory green lights to treat atrial fibrillation by late next year.

http://online.wsj.com/article/SB125167554221971053.html