Life-saving study results lift Bayer/J&J clot drug

Sun Nov 13, 2011 2:09pm EST

* Low-dose Xarelto cuts death risk more than 30 pct

* Trial tested drug in acute coronary syndrome

* Rival pill from Bristol/Pfizer fails separate study

* Merck's vorapaxar misses main goal, raises bleeding risk

By Bill Berkrot and Lewis Krauskopf

ORLANDO, Fla., Nov 13 (Reuters) - Data showing the life- saving benefits of a very low dose of a new blood clot preventer could alter future treatment of patients who suffer from acute coronary syndrome and provide a boost for the drug's makers Bayer AG and Johnson & Johnson .

Results of a large, late-stage clinical trial presented on Sunday showed the new pill, Xarelto, reduced the risk of death by more than 30 percent in patients who have had an ACS episode, typically a heart attack caused by a blocked coronary artery. Xarelto was added on top of blood thinners that are now the standard of care.

The Atlas study signals a new option for the estimated 1.2 million Americans treated for ACS each year and could open up a market worth up to $3 billion for the drug's manufacturers. The companies plan to seek approval for the use by year's end.

"We have seen with this trial a new standard of anti-thrombotic therapy emerge," said Dr. Paul Armstrong, professor of medicine at the University of Alberta, Edmonton, who provided commentary on the Xarelto trial at the American Heart Association scientific meeting in Orlando, where the study's details were unveiled.

Xarelto won the battle of new blood thinners at least on Sunday, as apixaban from Bristol-Myers Squibb and Pfizer , and Merck's vorapaxar each failed to meet the main goal of separate, unrelated studies presented at the meeting attended by thousands of doctors and researchers.

In the Atlas study of 15,526 patients, those who received 2.5 milligrams of Xarelto twice a day on top of current standard therapy had the risk of cardiovascular death cut by 34 percent and all causes of death by 32 percent compared to patients on Plavix and aspirin, or just aspirin.

"Until now we have only used anti-platelet therapy and now we have another class of drug that appears to provide additive benefit, so I think that is a landmark event," Dr. Raymond Gibbons of the Mayo Clinic said in an interview at the meeting.

Xarelto patients did have a significantly higher incidence of major bleeding, including intracranial bleeding, but no increase in fatal bleeds. Researchers said the lower death rate trumped the bleeding risk.

"You only have to treat 56 patients to save a life. It's hard not to be excited by the mortality benefit," said Dr. Michael Gibson, the study's lead investigator, who presented the results at the meeting.

"If it is approved (for this use) I think it will be widely adopted," Gibson said.

APIXABAN SETBACK

Xarelto, which inhibits a protein called Factor Xa involved in the blood clotting process, is vying for position with other new medicines in the multibillion-dollar anti-clot market, including apixaban and Pradaxa, which is sold by privately held German drugmaker Boehringer Ingelheim.

Earlier this month, Xarelto won U.S. approval for preventing strokes in patients with a dangerously irregular heartbeat called atrial fibrillation, considered to be by far the largest and most lucrative use for the new generation of blood thinners at an estimated $10 billion. Pradaxa is also approved in those patients.

Based on data from earlier studies in atrial fibrillation patients, apixaban has been widely viewed as the best of the new clot preventers. The Xarelto results in ACS patients could help to level the playing field somewhat as apixaban failed to help those patients in a prior study.

In data presented in Orlando, apixaban tackled seriously ill hospitalized patients at high risk of developing dangerous blood clots in the limbs and lungs. Xarelto suffered a setback in April when surprisingly high bleeding rates deemed the drug unacceptable for such patients.

Apixaban, which was compared to an older injected drug, enoxaparin, showed a trend toward improvement but came up short of achieving a statistically significant result.

Merck's vorapaxar was also tested in ACS patients, but proved to be no better in reducing a host of cardiovascular problems when added on top of aspirin and Plavix. It also increased the risk of bleeding, including tripling the risk of intracranial hemorrhage.

Researchers did find vorapaxar cut heart attacks, which they said warranted further study.

The drug's prospects already were dimmed after being deemed inappropriate for stroke patients in January, but Merck said it would wait until it has results from another large study early next year before deciding the medicine's fate.

Vorapaxar had been touted as the most important drug in Schering-Plough's experimental drug pipeline when Merck acquired its rival for $41 billion in late 2009.