Prasugrel and Dronedarone: Rough Roads to Approval

This past week or so was the week for the FDA to issue approvals of two drugs with tough paths to approval: prasugrel (marketed by Eli Lilly as "Effient®"), a potent platelet inhibitor used following acute coronary interventions and dronedarone (marketed by Sanofi-Aventis as "Multaq®"), an antiarrhythmic and cogener of amiodarone that does not contain Amiodarone's iodine molecule, which was approved for therapy of atrial flutter and atrial fibrillation is patients without severe congestive heart failure.

Prasugrel (Effient®)

Prasugrel is a thienopyridine — a prodrug that, like clopidogrel, requires conversion to an active metabolite before binding to the platelet P2Y12 receptor to confer antiplatelet activity. In the TRITON TIMI-38, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding while overall mortality did not differ significantly between treatment groups. The trial used a 60-mg loading dose, followed by a 10-mg maintenance dose administered after an acute coronary intervention. It seems that the concerns about bleeding did not escape the FDA's watchful eye, especially in lieu of the controversy surrounding the Cardiovascular and Renal Drugs Advisory Committee's decision to remove Sanjay Kaul, M.D., of Cedars-Sinai Medical Center in Los Angeles, an outspoken critic of the potential bleeding complications of the drug.

Dronedarone (Multaq®)

In 2006, the FDA shot down approval of dronedarone because of its limited effectiveness or safety, we weren't sure. In 2007 additional European data demonstrated efficacy and safety of the drug. In 2008 the drug was granted a reprieve by the FDA after the preliminary results of the Athena Trial that excluded patients with severe CHF were published and demonstrated a reduced incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation administered 400 mg twice a day of the medication compared to placebo.

Precisely when these drugs will be available to the general market is uncertain, but I suspect you'll know when meals start showing up in cath labs and offices again.

-Wes