Biotech Values

[DewDiligence]

LLY’s Prasugrel Bests Plavix in Phase-1 Trial of Clotting Time

[The data from this small study are very impressive, but approval of Prasugrel depends on the large phase-3 “outcomes” trials in progress. As Plavix is the world’s second largest-selling drug, Prasugrel is potentially a mega-blockbuster for LLY. Moreover, the use of antiplatelet therapy for stent patients may increase if it can be shown that longer therapy—and better compliance—can lick the “late thrombosis” problem that has caused doctors to rethink the risks of drug-eluting stents.]

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20061023:MTFH38671_2...

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Mon Oct 23, 2006 1:02 PM ET
By Bill Berkrot and Ransdell Pierson

NEW YORK, Oct 23 (Reuters) - A small study presented on Monday suggests Eli Lilly and Co.'s <LLY> experimental blood clot preventer, prasugrel, works faster and could be more effective than the commonly used double dosage of Plavix, the blockbuster anti-clot medicine.

Thirty-three healthy aspirin-free subjects completed the Phase I trial. Although not the heart-disease population for whom such a drug would eventually be used, the study may give an indication of how prasugrel could alter the competitive landscape for multibillion-dollar anti-clotting drugs.

"This data shows for the first time that as early as 30 minutes after dosing, a 60 milligram prasugrel loading dose achieves greater platelet inhibition than both the approved loading dose and high-dose clopidogrel (Plavix)," said the study's lead investigator, Kenneth Winters, a senior research cardiologist for Lilly, who presented the data on Monday at a medical meeting.

Plavix is the standard of care to prevent heart attacks in patients who receive stents to prop open heart arteries that have been cleared of plaque. The drug, which is taken along with aspirin, prevents blood clots by stopping sticky blood cells called platelets from clumping together.

Patients typically receive a 300-milligram starting dose, or "loading" dose, of Plavix when their stents are inserted. They then receive a daily 75 milligram dose…for three to 12 months afterward, to prevent heart attacks that can occur when clots develop in or near the implanted stent.

However, doctors frequently give patients a starting dose of 600 milligrams of Plavix -- twice the approved dose -- under the assumption it will work faster and produce more consistent anti-clot protection.

Lilly said its new trial suggests that, in terms of preventing platelet clumping, the standard 60-milligram starting dose of prasugrel shows clear superiority over the standard Plavix dose and over double dosages of Plavix. Clumping was assessed by a standard blood test.

Prasugrel, being co-developed with Japanese drugmaker Daiichi Sankyo Co. Ltd <4568.T>, is considered a crucial future source of profit growth for Indianapolis-based Lilly. Investors are eagerly awaiting crucial data from a Phase III, or late- stage trial, comparing the two drugs slated to be unveiled late next year.

According to the tiny Phase I study presented Monday at a heart research meeting in Washington, a 60-mg initial dose of prasugrel demonstrated inhibition of platelet aggregation -- a measure of anti-clotting prowess -- of 52.1 percent after just 30 minutes. That compared with 1.3 percent reduction in platelet clumping for the 300-mg Plavix loading dose and 4.3 percent reduction for Plavix at 600 mg.

Four hours after administration, prasugrel still had a much greater anti-clotting effect of 89.7 percent, compared with 64.1 percent for 600 mg of Plavix and 42.4 percent for the lower Plavix dose, researchers said. The results were deemed to be statistically significant.

Both drugs were tested on the same healthy patients for seven days each, with a two-week washout period between each arm of the study.

Winters said one shortcoming of Plavix is that it produces poor or variable platelet inhibition in about 20 percent to 30 percent of patients, thereby leaving them prey to blood clots that can cause heart attacks.

"With prasugrel we have seen essentially no poor responders," he said.

The separate Phase III trial, involving 14,000 patients with acute coronary syndrome, is designed to prove whether the Lilly drug is actually more effective than Plavix in preventing heart attacks, strokes and death.

Plavix, sold by Bristol-Myers and French drugmaker Sanofi-Aventis <SNY>, had global annual sales of about $6 billion last year, second only to Pfizer Inc.'s <PFE> cholesterol fighter, Lipitor.
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