Cangrelor regulatory update

FDA's Cardiovascular and Renal Drugs Advisory Committee voted against approval of an NDA for cangrelor from The Medicines Co. for both proposed indications. The panel voted 7-2 that cangrelor should not be approved to reduce thrombotic events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). The panel voted 9-0 that cangrelor should not be approved for patients with stents who are at increased risk for thrombotic events when oral P2Y12 therapy is interrupted due to surgery. The NDA has an April 30 PDUFA date.

Panel members were concerned with the design of the Phase III CHAMPION PHOENIX trial, including the definition of myocardial infarction (MI) and the allowance of a lower dose of clopidogrel in the control arm compared with the cangrelor arm. Cangrelor met the primary composite endpoint in the trial of reducing all-cause-mortality, MI, ischemia-driven revascularization and stent thrombosis at 48 hours vs. clopidogrel alone in patients undergoing PCI. The members also said there is uncertainty about the benefit/risk profile of cangrelor, noting that the compound missed the same composite endpoint using a different MI definition in 2 other Phase III trials. On the second indication, panel members said there were not enough data on the proposed dose, reiterating concerns raised by FDA reviewers in briefing documents released ahead of the meeting. ...