Cangrelor

Product Overview

Cangrelor is an investigational antiplatelet agent undergoing late-stage clinical development for intravenous use during coronary procedures (e.g., PCI) as well as the management of patients experiencing acute coronary syndromes. The safety and efficacy of Cangrelor is not established by the FDA for any use; however, studies are currently underway to examine the safety and efficacy of cangrelor.

Cangrelor was exclusively licensed in December 2003 from AstraZeneca. Under the terms of our agreement with AstraZeneca, The Medicines Company will have exclusive license rights to develop, market and sell cangrelor worldwide, excluding Japan, China, Korea, Taiwan and Thailand.

Clinical Trials Overview

In total, Cangrelor has been studied in approximately 400 patients in 6 phase I studies and 4 phase II studies to date.

Early Development

These early clinical studies consist of Phase II clinical trials of cangrelor conducted by AstraZeneca prior to licensing this product candidate to us, and a 40-person clinical trial that MDCO conducted in healthy volunteers to identify a dosing strategy for use of cangrelor. [1,2]

Based on input from our hospital customers in the cardiac catheterization laboratory, there may be limitations in current oral therapies in the acute care setting which may include delayed onset, prolonged effect and unpredictable effect. This has created a need for an intravenous platelet inhibitor that acts quickly, is cleared from the bloodstream rapidly and enables rapid recovery of platelet function.

Phase III Clinical Trials

The phase III program for Cangrelor is underway and currently consists of two large studies with a combined planned total enrollment of 15,400 patients.

The CHAMPION-PCI study, which commenced enrollment in March 2006, is designed to enroll approximately 9,000 patients. The primary objective of this study is to demonstrate that the efficacy of cangrelor is superior, or at least non-inferior, to that of clopidogrel in subjects requiring PCI as measured by a composite of all-cause mortality, myocardial infarction (MI), and ischemia driven revascularization (IDR). The incidence of hemorrhage by clinically relevant criteria (ACUITY, GUSTO, TIMI) and the need for blood transfusions will also be measured up to 48 hours. Patients in this trial may be treated with other intravenous anticoagulants, such as bivalirudin, heparin and GP IIb/IIIa inhibitors, at the investigator’s discretion.

The 2nd trial in the phase III program is referred to as CHAMPION-PLATFORM, which commenced enrollment in October 2006 and is designed to enroll approximately 6,400 patients. The primary objective of this study is to demonstrate that the efficacy of cangrelor (combined with usual care) is superior to that of usual care, in subjects requiring PCI, as measured by a composite of all-cause mortality, MI, and IDR. The incidence of hemorrhage by clinically relevant criteria (ACUITY, GUSTO, TIMI) and the need for blood transfusions will also be measured up to 48 hours. Patients in this trial may also be treated with other intravenous anticoagulants, such as bivalirudin, heparin and GP IIb/IIIa inhibitors, at the investigator’s discretion.

Mechanism of Action

Cangrelor, formerly denoted as AR-C69931MX, is a short-acting, potent, competitive P2Y12 platelet receptor antagonist. P2Y12 receptors are highly expressed on the surface of platelets and cangrelor is specific for this receptor. [3] 

References:

1. Data on File, The Medicines Company
2. Greenbaum AB, Grines CL, Bittl JA, et al. Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial. Am Heart J. 2006;151:689.e1-689e10.
3. Nassim MA, Sanderson JB, Clarke C, et al.  Investigation of the novel P2T receptor antagonist AR C69931MX on ex vivo adenosine diphosphate induced platelet aggregation and bleeding time in healthy volunteers.  J Am Coll Cardiol. 1999;33(2 Suppl A):255A