Lilly clot drug linked to more bleeding in trial (Reuters)

The widely anticipated findings of Lilly and Daiichi Sankyo Co's (4568.T) bid to take on Bristol-Myers Squibb's (BMY.N) Plavix also found the drug, called prasugrel, was significantly more effective in limiting death from cardiovascular events, nonfatal heart attack and strokes.

But the excess bleeding seen with the drug, tested in heart patients with symptoms from severe chest pain to heart attacks, could hurt its chances for regulatory approval and hoped-for blockbuster sales, according to analysts.

The 13,600-patient trial found 2.4 percent of patients on prasugrel suffered at least one major bleeding event, compared with 1.8 percent of patients on Plavix, which Bristol markets with Sanofi-Aventis (SASY.PA).

"When it comes to anti-clotting medications, there is no free lunch," said Deepak Bhatt, cardiologist and professor of medicine at the Cleveland Clinic, who wrote the editorial accompanying the study. "In order to reduce heart attack risk, there is a trade-off with increased bleeding," Bhatt, who has received consulting and other fees from drugmakers on both sides of the trial, said in an interview.

Results were published in a special issue of the New England Journal of Medicine, timed for release at the American Heart Association's annual meeting in Orlando, Florida.

Analysts had been fretting that prasugrel would cause more bleeding in the trial, called Triton, especially after Lilly in recent weeks stopped giving the drug to patients in two small trials without fully explaining its reasons.

"Prasugrel needs to show a net improvement in overall risk/benefit profile, i.e. superior efficacy, without increased bleeding risk, to justify approval, in our view," Bear Stearns analyst John Boris wrote in an investor note prior to the release of the results.

SEEKING TO CHALLENGE PLAVIX

Lilly and Daiichi have been developing prasugrel in hopes it will become an alternative to Plavix, a drug with combined $6.5 billion in annual sales for Bristol and Sanofi that makes it one of the world's top-selling medicines.

Both Plavix and prasugrel prevent clots by keeping blood cells called platelets from sticking together.

Despite the bleeding risk, Bhatt also said the study is important because it validates the "more is better" approach to preventing blood clots in patients with heart disease.

"This is the first validation that more powerful oral anti-platelet drugs further reduce coronary complications," Bhatt said.

Prasugrel proved significantly better at limiting death from cardiovascular causes, nonfatal heart attacks or strokes. About 9.9 percent of prasugrel patients suffered one of those events, compared with 12.1 percent among the Plavix group.

Patients on prasugrel also had significant reductions in heart attack, urgent surgeries and blood clots within stents, tiny mesh tubes used to prop open arteries.

In the editorial, Bhatt noted the study's analysis of sub-groups that might be most harmed from the drug. Those groups include those at high risk of bleeding to begin with, older patients and those with low body weight.

Excluding such high-risk patients could mitigate the drug's risks, he said.

However, post-study analysis usually carries much less weight with regulators than statistical trial results based on previously specified study goals.

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