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AstraZeneca Developing Reversal Agent for Its Own Heart Drug, Brilinta (Ticagrelor)
AstraZeneca has begun a preclinical development program to evaluate the ability of an investigational antibody, MEDI2452, to rapidly and specifically reverse the antiplatelet effects of ticagrelor (Brilinta) in rare emergency situations, such as urgent surgery, or in the event of major bleeding.
MEDI2452 is a neutralizing antibody that binds to ticagrelor and AR-C124910XX, the ticagrelor active metabolite, and is intended to reverse the antiplatelet effects of ticagrelor. The treatment is being developed by MedImmune, AstraZeneca’s biologics research-and-development arm.
The development of MEDI2452 coincides with the wider PARTHENON clinical program for ticagrelor, which includes five registration studies involving approximately 80,000 patients with atherothrombotic disease. The PEGASUS-TIMI 54 trial, involving more than 21,000 patients, will be the next study in the program to reach completion, with top-line results expected in the first quarter of 2015. The trial’s objective was to assess the efficacy and safety of ticagrelor (administered twice daily) compared with placebo on a background of low-dose aspirin for the long-term prevention of atherothrombotic events in adults (50 years of age or older) who experienced a heart attack 1 to 3 years before study enrollment, and who had one additional cardiovascular risk factor.
Ticagrelor is an oral antiplatelet treatment for acute coronary syndrome (ACS). It is a direct-acting P2Y12 receptor antagonist and is the first in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs), providing a treatment option to the thienopyridine class of oral antiplatelets. Ticagrelor works by inhibiting platelet activation and has been shown to reduce the rate of thrombotic cardiovascular (CV) events, such as a heart attack or CV death, in patients with ACS.
Currently, no FDA-approved medications are available to counteract the antiplatelet effect of ticagrelor.
Source: AstraZeneca; November 13, 2014.