The US Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee voted 9 to 0 that prasugrel, an investigational antiplatelet agent, should be approved for the treatment of patients with acute coronary syndromes (ACS) managed with an artery-opening procedure known as percutaneous coronary intervention (PCI), Daiichi Sankyo Company, Limited, and Eli Lilly and Company announced.
The Advisory Committee voted unanimously that prasugrel should be approved for the treatment of patients with acute coronary syndromes undergoing PCI. The FDA is not bound by the committee's recommendation, but it takes its advice into consideration when reviewing new drug applications.
"We are very proud of the prasugrel data," said John Alexander M.D., M.P.H., global head of research and development, Daiichi Sankyo Company, Limited. "Today's scientific exchange set the stage for a potential FDA approval of prasugrel, and the future availability of this significant scientific advancement for the treatment of ACS-PCI patients."
"We will continue to work closely with the FDA as the agency moves toward an action on the new drug application for prasugrel," said J. Anthony Ware, M.D., Lilly vice president and cardiovascular/acute care platform leader for prasugrel. "It is important for patients to have multiple treatment options, and currently, ACS patients undergoing PCI have few options. Today's vote by the advisory committee members is a positive step for patients."
"Prasugrel represents an important new option for patients with ACS who are managed with PCI," said lead TRITON-TIMI 38 investigator Elliott Antman, M.D., director of the Samuel A. Levine Cardiac Unit at Brigham and Women's Hospital (BWH) in Boston and senior investigator with BWH's TIMI Study Group. "In a large head-to-head trial, TRITON, showed that prasugrel was superior to clopidogrel, the current standard of care. While the benefit of prasugrel is accompanied by an increased risk of serious bleeding events, appropriate selection of patients and doses may help mitigate this risk."
The committee reviewed comprehensive data primarily from the TRITON TIMI- 38 clinical trial. Results from the TRITON trial showed that prasugrel taken with aspirin reduced the relative risk of the combined endpoint of cardiovascular death, non-fatal heart attacks or non-fatal stroke by 19 percent more than clopidogrel (Plavix/Iscover taken with aspirin.
These benefits were accompanied by an increased risk of serious bleeding with prasugrel overall, some of which included life-threatening and even fatal bleeding. When the risk of this type of bleeding was compared to the benefit of reduced heart attack, there were five more TIMI major bleeding events, but 22 fewer heart attacks for every 1,000 patients treated with prasugrel compared to every 1,000 patients treated with clopidogrel. The overall risk of cardiovascular death and the risk of increased stroke were not statistically different between treatment groups.
FDA reviewers will consider the panel's favourable recommendation in its review of the new drug application that Lilly submitted for prasugrel on behalf of the alliance with Daiichi Sankyo, Limited, on December 26, 2007.
Acute coronary syndromes (ACS), which includes heart attack and unstable angina (chest pain), affects more than 1.4 million people in the United States annually. Coronary heart disease, which can result in ACS, is the single most common cause of death in the European Union, accounting for more than 741,000 deaths in the EU each year.
Coronary artery disease occurs when the arteries become narrowed or clogged by cholesterol and fat deposits and cannot supply enough blood to the heart. In some cases, a blood clot may partially or totally block the blood supply to the heart resulting in ACS. Many ACS patients are managed with PCI, which usually includes a stent placement.
Daiichi Sankyo Company, Limited, and Eli Lilly and Company are co-developing prasugrel, an investigational oral antiplatelet agent discovered by Daiichi Sankyo and its Japanese research partner, Ube Industries, Ltd., as a potential treatment, initially for patients with acute coronary syndromes who are managed with PCI.
Prasugrel works by inhibiting platelet activation and subsequent aggregation by blocking the P2Y12 adenosine diphosphate (ADP) receptor on the platelet surface. Antiplatelet agents prevent platelets from clumping or sticking together, which can result in clogged arteries and may lead to heart attack or stroke.