June 3, 2009
Antiplatelet Medication Is Unsafe, Should Not Be Approved, Says Scientist Who Helped Develop the Drug
Researcher Joins Public Citizen in Asking FDA to Halt Drug Review
WASHINGTON, D.C. – One of the scientists who holds a patent application for the blood clot inhibitor prasugrel hydrochloride, an acute coronary syndrome (ACS) treatment, wants the Food and Drug Administration (FDA) to reject the drug because it is neither safe nor effective, according to a joint letter he and Public Citizen sent to the FDA today.
The letter to FDA Commissioner Dr. Margaret Hamburg asks the FDA to halt its review of prasugrel, citing serious flaws in TRITON-TIMI 38, the Phase 3 clinical trial that compared prasugrel to clopidogrel, another platelet inhibitor, in patients with ACS. The letter was signed by Dr. Victor Serebruany, who is a patent application holder for prasugrel and who worked on early clinical studies for the drug; Dr. Sidney Wolfe, Public Citizen’s acting president and director of its Health Research Group; and Dr. James Floyd, a Public Citizen researcher.
Perhaps the greatest problem in TRITON-TIMI 38 was the incorrect and unsafe dose of prasugrel used. As early as May 2004, Serebruany told drug maker Eli Lilly and Company and investigators conducting the study that the 10 milligram daily dose of prasugrel they were planning to use was about 2.5 times more potent than the dose of clopidogrel used in the study, and that a much lower dose of prasugrel should be studied.
TRITON-TIMI 38 revealed a dramatic increase in the risk of hemorrhage and an unexpected increase in new cancers among patients on prasugrel when compared to those on clopidogrel. While prasugrel does not appear to be a carcinogen, it may act as a cancer promoter through its excessive antiplatelet activity, diminishing the natural capacity of platelets to halt the spread of locally confined or “silent” tumors, the letter said.
“An earlier clinical study showed that a 10 milligram daily dose of prasugrel was far too potent, and I raised concerns that it might result in an increased bleeding risk,” said Serebruany, who has sold commercial licensing rights for the patent to Eli Lilly. “This is exactly what was seen in the TRITON-TIMI 38 study. Considering that bleeding rates grow over time, the effects of this drug could be even worse in real-life scenarios.”
In addition to these safety concerns, the effectiveness of prasugrel is in question because the design of the study favored it unfairly, and many of the supposedly bad outcomes the drug prevented were not medically important.
“The risks of hemorrhage and possibly cancer far outweigh the need to introduce prasugrel to the market – not when the efficacy of this drug is in question and other approved antiplatelet medications are already available to patients,” Floyd said. “At a lower dose, prasugrel may, indeed, be a useful antiplatelet drug, but until a new Phase 3 study can be conducted with an appropriate dose, we urge the FDA to stop its current review of this drug.”