Johns Hopkins University Professor Victor L. Serebruany, MD, PhD, an investigator in prasugrel's early clinical trials assessment, and two consumer advocates at Public Citizen have petitioned the FDA to halt its ongoing regulatory review of the anticoagulant, and requested new studies with a lower dose be launched.

The Division of Cardiovascular and Renal Products is currently reviewing new drug application 22-307, prasugrel hydrochloride (Efient from Eli Lilly/Daiichi Sankyo) for use in acute coronary syndrome (ACS).

In a letter to FDA Commissioner Margaret Hamburg, MD, Serebruany disclosed that he is a paid U.S. patent application holder for prasugrel and worked on early clinical studies of prasugrel. However, he and Public Citizen advocates James Floyd, MD, and Sidney Wolfe, MD, urged the FDA to "halt its review of prasugrel for possible approval until a properly-designed Phase 3 study has been performed with a lower, safer dose of prasugrel and properly defined clinical outcomes."

Serebruany, Floyd and Wolfe said they have previously raised concerns about the efficacy and safety of prasugrel, as well as the "serious flaws" of TRITON-TIMI 38, the phase 3 study comparing prasugrel with clopidogrel (Plavix from Bristol-Myers Squibb) with an appropriate lower dose of prasugrel and properly defined outcomes in patients with ACS.

In October 2008, Serebruany spoke with Cardiovascular Business News about similar concerns regarding the drug's dose.

In the recent letter, they said that the 10 mg dose of prasugrel could risk hemorrhaging, and may promote the development of cancer. The doctors requested that the developers study a 5 mg dose.

"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 doctors wrote. They also noted that TRITON-TIMI 38 did not test two uniquely different methods of platelet inhibition in the setting of ACS.

Lilly told Dow Jones Newswire that a study of a lower dose is underway but will not be completed before 2011.

The authors concluded that the "available evidence suggests that prasugrel at a daily dose of 10mg is unsafe, resulting in excess hemorrhage and perhaps cancer. The efficacy of the drug is also in question."