AstraZeneca has begun a pre-clinical development programme to evaluate the ability of 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 being developed by MedImmune, AstraZeneca’s biologics research and development arm.
“In certain emergencies, doctors need to have the option to swiftly reverse the effects of oral antiplatelet agents, in order to enable emergency surgery or a quick response to a major bleeding event without having to wait for the effects of the medicine to wear off. Currently there are no FDA approved medications to counteract the antiplatelet effect in these situations,” said Marc Ditmarsch, Global Development Lead for Brilinta. “If the circumstances demand it, we believe MEDI2452 has the potential to help address this need for patients treated with Brilinta.”
The development of MEDI2452 sits alongside the wider PARTHENON clinical programme for Brilinta, which includes five registration studies involving around 80,000 patients across the broad spectrum of atherothrombotic disease. The PEGASUS-TIMI 54 study, involving more than 21,000 patients, will be the next study within the programme to complete, with top line results expected in the first quarter of 2015. PEGASUS-TIMI 54 aims to assess the efficacy and safety of ticagrelor (twice daily compared to placebo on a background of low-dose aspirin), for the long-term prevention of atherothrombotic events in patients, aged 50 and older, who suffered a heart attack one to three years prior to study enrolment, and who have one additional cardiovascular risk factor.
“Current guidelines generally recommend 12 months of dual antiplatelet therapy following an acute coronary syndrome event, however atherothrombotic disease is a chronic, progressive and in some cases fatal condition,” Marc Ditmarsch continued. “The PEGASUS trial will help us evaluate the potential long-term benefit of therapy with ticagrelor for the chronic condition. This will be important information for patients with a history of myocardial infarction and their physicians, to determine the management of their condition following a heart attack beyond 12 months.”
The initiation of the development programme for MEDI2452 comes ahead of the AHA Scientific Sessions, taking place in Chicago from 15-19 November 2014. AstraZeneca will present nine abstracts across its pipeline and marketed products at the meeting, as well as showcasing its strength in cardiovascular and metabolic diseases as a core therapy area.
Results from a study comparing pharmacodynamic profiles of escalating loading dose regimens of Brilinta, in patients with ST-elevation myocardial infarctions, Sunday 16 November, 2014.
Data from the EVOLVE study, analysing the effect of EPANOVA on apolipoprotein CIII (a protein known to promote dyslipidemia) concentrations in high, low and very low density lipoproteins, in patients with moderate to severe hypertriglyceridemia,. Sunday 16 November, 2014.
Data from the JUPITER trial looking at lipoprotein subclass and size changes in response to treatment with CRESTOR, in order to identify predictors of diabetes, Monday 17 November, 2014.
The AHA Scientific Sessions come at a significant time for Brilinta, with the recent update to the AHA and American College of Cardiology guidelines for the management of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), which will also be discussed at the meeting. The guidelines support differentiation among currently available P2Y12 inhibitors, including Brilinta, clopidogrel and prasugrel for these patients. In a Class IIa recommendation, Brilinta is now preferred over clopidogrel for the management of NSTE-ACS patients who undergo an early invasive (angiography with intent for percutaneous coronary intervention, if appropriate), ischaemia-guided (i.e. medically managed) strategy, or those who receive a coronary stent.