FDA says NO to Cangrelor

FDA Advisory Panel Votes Against Cangrelor Approval
In a recent ruling, the USFDA advisory panel consisting of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted against approving cangrelor, in the PCI setting and in the Bridging setting. The Medicines Company was seeking approval of cangrelor, a potent antiplatelet intravenous adenosine diphosphate (ADP)–receptor antagonist that has a rapid onset of action with quick reversible effects. However, the company press release also mentined that the committee recommendation was “not binding on the FDA, which makes the final decision on approval.” The Prescription Drug User Fee Act (PDUFA) goal date for the cangrelor new drug application (NDA) is April 30, 2014.

Cangrelor background

In the PCI setting, cangrelor has led to a reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). In the Bridging setting, P2Y12 inhibition was maintained in patients with acute coronary syndromes or patients with stents who are at increased risk for thrombotic events (such as stent thrombosis) when oral P2Y12 therapy is interrupted due to surgery. The drug was considered a boon for interventional cardiologists since the clinical effects persisted for about an hour after an infusion stopped, as opposed to days following a dose of an oral antiplatelet drug like clopidogrel or ticagrelor (5 days), prasugrel (7 days).

Antiplatelet therapy during PCI forms the foundation in evading PCI-related ischemic complications. Clinical trials conducted for safety and efficacy of cangrelor has had mixed results. The CHAMPION PLATFORM trial was prematurely stopped due to the lack of superiority compared to clopidogrel in patients undergoing PCI. When rates of stent thrombosis were compared in the CHAMPION PCI trial, no significant difference was observed between cangrelor and clopidogrel at 48hrs and the trial discontinued.However, investigators designed the CHAMPION PHOENIX clinical trial, from observations of PLATFORM and PCI trials, concluded that cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, as compared to clopidogrel at 48hrs. What was clinically important was the adverse events noted in the PHOENIX trial. Bleeding related deaths were (2 vs. 4) with cangrelor compared to clopidogrel and numerically more clinically important bleeding events of intracranial hemorrhage (3 vs. 2), cardiac tamponade (9 vs. 1), retroperitoneal bleeds (7 vs. 3) and gastrointestinal bleeds (16 vs. 10) among cangrelor-treated patients. Pooled data demonstrated that mild dyspnoea was reported more with cangrelor use when compared to controls (1.2%vs 0.4%) and was the cause for the discontinuation of the drug.
In patients at high risk for thromboembolic events awaiting surgery, the BRIDGE trial confirmed cangrelor use provided consistent inhibition of platelet reactivity during infusion. Cangrelor was associated with a numerical increase in non–CABG-related bleeding occurring during the 5 to 7-day bridging period while the infusion was still being administered. The results confirmed continued P2Y12 inhibition even shortly before surgery to lower the risk of thrombotic events, with rapid return of platelet function to lower the risk of surgical bleeding.
Source
http://ir.themedicinescompany.com/phoenix.zhtml?c=122204&p=irol-newsArticle&ID=1899593&highlight=

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