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FDA Committee Issues Mixed Opinions on Blood Clot Drug Cangrelor
Team leader recommends against approval (February 10)
Members of the FDA’s Cardiovascular and Renal Drugs Advisory Committee are divided on whether cangrelor (The Medicines Company), an intravenous anticoagulant, should receive marketing approval.
Medical team leader Thomas A. Marciniak, MD, has recommended that the drug be rejected, saying that the clinical data do not support the superiority of cangrelor over a rival treatment, clopidogrel (Plavix, GlaxoSmithKline). Another reviewer, however, stated that cangrelor should be approved.
The opinions were posted 2 days ahead of a meeting of outside experts who will make their own recommendation. The FDA is not required to follow the advice of its advisory panels but typically does so.
Cangrelor is a new platelet inhibitor studied for use with percutaneous coronary intervention (PCI) for the treatment of stable angina or acute coronary syndromes (ACS, or myocardial infarction [MI] and unstable angina [UA]). Like clopidogrel, cangrelor is a platelet P2Y12 receptor inhibitor. Unlike orally administered clopidogrel, however, cangrelor is administered intravenously and is a reversible rather than an irreversible inhibitor.
Marciniak concluded that the available clinical trial data do not demonstrate either the superiority or noninferiority of a cangrelor regimen compared with a clopidogrel regimen or with standard of care for the following reasons:
- Clopidogrel administration was delayed inappropriately in all of the pivotal clinical trials. The studies themselves provided evidence that earlier administration of clopidogrel was more effective than cangrelor, according to Marciniak.
- The cangrelor regimen was significantly superior only for the sponsor’s primary endpoint, which included predominantly “chemical” MIs.
- In the pivotal PHOENIX trial, only a 300-mg loading dose was allowed in the clopidogrel arm. The exclusive use of a 600-mg loading dose in the cangrelor arm may explain some of the “superiority” of that arm, Marciniak notes.
- The “superiority” of cangrelor was statistically significant only in the stable angina subgroup, and yet stable angina is the condition for which cangrelor offers minimal advantages, if any.
- The data suggest the possibility of harm with cangrelor in patients with ST-segment elevation MI (STEMI).
- The pivotal trials demonstrated an increased risk of bleeding with cangrelor compared with clopidogrel.