“This has not been a well managed review process” –FDA official on prasugrel approval

A month after approving prasugrel the FDA has released some, but not all, of the documents it is required to post on its website. According to knowledgeable observers, the full action document has not yet been released.

CardioBrief has not reviewed these documents in detail, but noticed a few items that might be of interest to readers:

Norman Stockbridge, director of the division of cardiovascular and renal products, states what has long been obvious to almost anyone observing the approval process:

This has not been a well managed review process. The issues were pretty clear early enough to have allowed us to meet the original PDUFA goal. What has been missing is a clear means or will to declare an end to discussions and to allow the regulatory process to complete. No one associated with this review should feel good about this.[p 5, Division Director Memo]

Stockbridge also discusses the highly inflammatory issue of Sanjay Kaul’s disinvitation from the advisory panel:

Dr. Sanjay Kaul was excluded from the Advisory Committee meeting for prasugrel, on the basis that he had published numerous analyses of the TRITON data. The lateness of the subsequent process is regrettable. Dr. Kaul gave his perspective on TRITON at a meeting on 24 April 2009 with Drs. Jenkins and Temple and many of the reviewers. He presented a number of novel analyses along the lines of his published abstracts, but he raised no issues that had not been thoroughly discussed by the review team. Many of his conclusions are compatible with those expressed in this memo and in draft labeling. However, he believes the clinical importance of even minor bleeding events to be at least similar to that of many of the enzyme-only MI events in TRITON, and he finds the cancer data to be a credible risk. Although he declined to opine whether prasugrel should be approved, he feels that use beyond a few weeks should be discouraged. [Division Director Memo, p 5]

Finally, Robert Temple, director of the Center for Drug Evaluation and Research, discussed the cancer findings in the review:

Although no one in the Division of Cardiovascular and Renal Products believes the cancer findings should block approval, Dr. Marciniak believes the finding merits restriction of use to one month. This was at least partly because the mouse hepatic adenoma and carcinoma data convinced him that prasugrel may have the ability to stimulate tumor growth, the cardiovascular event rate diminishes with time, and the advantage of prasugrel relative to clopidogrel wanes over time. For the reasons given by Dr Unger, and additional considerations described below, I do not believe that would be appropriate. [Office Director Memo, p 14]

You can access all the FDA documents by clicking on this link and searching for “prasugrel.” (Why is it that every time I spend time on the FDA website I feel I might get attacked by a minotaur?) Or you can click on this link, which links to most of the same documents but does not include links to the Medication Guide or the REMS (Risk Evaluation and Mitigation Strategy) document.

Click here for a complete chronology of the prasugrel controversy.


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  1. […] “This has not been a well managed review process” –FDA official on prasugrel approval (CardioBrief, August 11) […]

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