= 2nd UPDATE: Doctor Calls On FDA To Stop Prasugrel Review
June 03 2009 - 4:41PM
Dow Jones News
WASHINGTON (Dow Jones)--A doctor who was involved in early
clinical studies of prasugrel, an anti-clotting drug being
developed by Eli Lilly & Co. (LLY) and Daiichi Sankyo Co.
(4568.TO), said the Food and Drug Administration should stop its
review of the product and require the companies to conduct
additional studies of a lower dose.
The doctor, Victor Serebruany of Johns Hopkins University in
Baltimore, outlined his concerns that included bleeding risks, in a
letter sent to FDA Commissioner Margaret Hamburg Wednesday.
Serebruany is listed as one of the inventors on a patent
application for prasugrel, but later sold his rights to Eli Lilly.
The application is pending.
Serebruany said the proposed 10-milligram dose of the drug
causes excess bleeding and that a lower 5-milligram dose of the
drug should be tested. He also questioned the data that showed
prasugrel was better than another drug, Plavix, at cutting
heart-attack rates.
The FDA review of prasugrel has dragged on for more than a year.
An FDA spokeswoman confirmed the agency received the letter, but
said federal law prohibits the agency from commenting on the status
of drug applications pending at the agency. In February, an FDA
panel recommended the agency approve prasugrel after a generally
positive review from FDA staff.
The letter was also signed by two doctors from the consumer
advocacy group Public Citizen, including Sidney Wolfe. Wolfe is the
director of Public Citizen's health research group and also serves
on the FDA's drug safety advisory panel.
In a statement, Lilly and Daiichi Sankyo said the companies
remained "confident in the overall benefit-risk profile of
prasugrel and stand behind the clinical trial design and results."
The companies said they were in the "final" stages of the
drug-review process with the FDA but couldn't speculate on the
outcome. The main clinical trial, involving more than 13,000
patients, submitted to the FDA in support of prasugrel showed it
was better than 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.
The FDA review of the study showed that compared with Plavix,
which is comarketed by Bristol-Myers Squibb Co. (BMY) and Sanofi
Aventis SA (SNY), 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."
Serebruany raised several concerns about how prasugrel and
Plavix were given to patients in the trial and whether it offered a
fair comparison between the drugs. He also wrote the benefit of
prasugrel at reducing heart attacks was driven by a reduction in
non-fatal heart attacks and noted the definition of certain types
of heart attacks has changed since the trial was conducted.
Last month investigators for the prasugrel trial reanalyzed the
data according to the new heart-attack standards and found
prasugrel still cut heart-attack rates compared to Plavix, although
at somewhat lower rates than originally seen.
Lilly has said the company is studying a lower dose of prasugrel
but the study won't be complete until 2011.
Serebruany also spoke at the FDA advisory panel on prasugrel and
raised questions about the safety and effectiveness of the drug. At
the time he said he's received grants from Lilly, Bristol and
Sanofi. Serebruany also said he's been a consultant for
Bristol-Myers, Sanofi, Bayer AG (BAY) and a unit of Johnson &
Johnson (JNJ).
-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294;
jennifer.corbett@dowjones.com