Prasugrel approved with restricted label

July 10, 2009

Eli Lilly’s drug prasugrel, to be branded as Effient, was approved with a restricted label as we predicted (label attached).

• It seems the label will not allow a claim of superiority over Plavix. Recall, the TIMI trial was designed to show this.
• Black box warnings were added that were not voted on by the advisory panel (sans Dr. Kaul and the OSE). Importantly, the frail elderly woman type of patient (older than 75 and less than 60KG), is a black box warning. Patients that might need heart surgery, CABG, are also in the warning.

· Connection to cancer risk is in the label with post-approval data collection required

It is no surprise to us that this news was released on a Friday with no company conference call to our knowledge. A common tactic is to release bad news on Friday evenings. In addition, per our previous note today, the FDA response to the congressional oversight investigation into the prasugrel advisory panel and admitted mistakes in handling of the matter.

FDA NEWS RELEASE

For Immediate Release: July 10, 2009

FDA Approves Effient to Reduce the Risk of Heart Attack in Angioplasty Patients

The U.S. Food and Drug Administration has approved the blood-thinning drug Effient tablets (prasugrel) to reduce the risk of blood clots from forming in patients who undergo angioplasty, a common procedure to unblock a clogged coronary artery.

During an angioplasty, a balloon is used to open the artery that has been narrowed by atherosclerotic plaque. Often, a tiny wire mesh scaffold (stent) is inserted into the blood vessel to help keep the artery open after the procedure. Platelets in the blood can clump around the procedure site, causing clots that can lead to heart attack, stroke, and death.

Effient was studied in a 13,608-patient trial comparing it to the blood-thinning drug, Plavix (clopidogrel), in patients with a threatened heart attack or an actual heart attack who were about to undergo angioplasty.

The fraction of patients who had subsequent non-fatal heart attacks was reduced from 9.1 percent in patients who received Plavix to 7.0 percent in patients who received Effient. While the numbers of deaths and strokes were similar with both drugs, patients with a history of stroke were more likely to have another stroke while taking Effient. In addition, there was a greater risk of significant, sometimes fatal, bleeding seen in patients who took Effient.

“Effient offers physicians an alternative treatment (The HCC note: not a superior treatment compared to Plavix) for preventing dangerous blood clots from forming and causing a heart attack or stroke during or after an angioplasty procedure,” said John Jenkins, M.D., director of the Office of New Drugs, in the FDA’s Center for Drug Evaluation and Research. “Physicians must carefully weigh the potential benefits and risks of Effient as they decide which patients should receive the drug.”

The drug’s labeling will include a boxed warning alerting physicians that the drug can cause significant, sometimes fatal, bleeding. The drug should not be used in patients with active pathological bleeding, a history of mini-strokes (transient ischemic attacks) or stroke, or urgent need for surgery, including coronary artery bypass graft surgery.

Effient is manufactured by Eli Lilly and Company of Indianapolis, in partnership with Tokyo-based Daiichi Sankyo Ltd.