Biotech Values

[DewDiligence]

Prasugrel briefing doc: I don’t see why analysts are talking about
an unduly narrow label inasmuch as the restrictions cited in the
briefing doc are the same ones LLY itself has proposed.

http://online.wsj.com/article/SB123332883610833547.html

›FDA Reviewers Recommend Agency Approve Prasugrel

By JENNIFER CORBETT DOOREN
JANUARY 30, 2009, 5:57 P.M. ET

WASHINGTON -- Food and Drug Administration medical reviews released Friday said the agency should approve Prasugrel, a proposed anticlotting drug being developed by Eli Lilly and Co. and Daiichi Sankyo Co., but should carry tough warnings about bleeding and cancer risks.

Reviews of Prasugrel by different FDA divisions were posted on the agency's Web site Friday. The drug faces a review Tuesday by medical experts who serve on the agency's cardiovascular and renal drugs advisory committee.

The panel is being asked to recommend if Prasugrel should be approved for use in certain patients at risk for a heart attack and, if so, what warnings should be placed on the drug.

Prasugrel is designed to keep blood platelets from sticking together to form dangerous blood clots that can cause heart attacks and strokes. If approved, Prasugrel would initially be used in heart patients undergoing a procedure known as percutaneous coronary intervention to open clogged arteries. PCI is usually followed by the placement of a stent.

One of the clinical trials involving more than 13,000 patients submitted to the FDA in support of Prasugrel showed it was better than another drug, Plavix, at preventing life-threatening blood clots in heart patients, but it was also associated with a higher risk of dangerous bleeding in some patients.

"This new advance in treatment is accompanied by an increase in bleeding events, but there is net clinical benefit in the overall trial population," Lilly said in documents also posted to the FDA's Web site.

The bleeding risk is likely to be a major focus of the panel meeting.

Analysts said the FDA review suggests Prasugrel would initially be approved for use in a relatively narrow segment of patients compared to the approved indications for Plavix.

"It looks like the FDA is willing to approve it but it has massive amounts of restrictions in there," said Natixis Bleichroeder analyst Jon LeCroy. "It's sort of a win-lose situation."

The FDA said, in a list of questions the panel is being asked to vote on, the study showed that for 1,000 patients treated with Prasugrel compared with Plavix, Prasugrel would prevent an additional 20 heart attacks and two cardiovascular-related deaths but would likely result in two fatal bleeding events and four life-threatening bleeding events. An agency reviewer said the drug carried a "worthwhile risk-benefit profile."

The agency said the bleeding risk could be reduced, but not eliminated, if Prasugrel is restricted to use in patients age 75 and younger and those without a prior history of stroke. The agency noted serious bleeding events increased in older patients and also said "moreover Prasugrel's efficacy is less certain in patients age 75 or greater."

Lilly is proposing using a 5-milligram dose of the drug -- rather than a 10-milligram dose -- in patients older than 75 and those who weigh less than 60 kilograms, or about 132 pounds. However, the FDA noted that only the 10-milligram dose was studied. Lilly is currently studying the lower dose as part of an ongoing clinical trial that's expected to be complete in 2011.

Along with the bleeding risk, the FDA said cancer was more commonly reported in the Prasugrel group but it's not clear if the drug played any role. The agency said the cancer issue needs to be addressed in additional post-market studies.

In a statement, a Daiichi Sankyo Inc. spokeswoman said "oncology experts, both internal at our companies, as well as external experts, have looked at our data very carefully, and we concluded that it is not biologically plausible that Prasugrel promotes tumor growth."

Last month, a European Medicines Agency committee issued a positive opinion recommending approval of Prasugrel. That opinion will be forwarded to the European Commission, which grants approval for drugs in the European Union. The commission usually follows that agency's advice.‹