PB1371 Platelet Activation with the Aeson Bioprosthetic Total Artificial Heart: Insight from Aspirin Treatment and Outcomes

Background: Platelet glycoprotein VI (GPVI) is a promising target to develop novel antithrombotic drugs combining efficacy and safety.Glenzocimab, a humanized antibody fragment, blocks GPVI activation by its major ligands, collagen and fibrin(ogen).The safety of glenzocimab alone has been demonstrated in healthy subjects.Aims: To establish the safety of glenzocimab in patients exposed to antithrombotic and fibrinolytic drugs.Methods: Non-Human Primate studies: Alteplase is the standard of care (SOC) for acute ischemic stroke (AIS) but the use of Tenecteplase (TNK) is increasing.Glenzocimab was coadministered with alteplase or TNK at nonobservable adverse effect levels in toxicity studies in cynomolgus monkeys Clinical Trials: The safety analysis of two clinical trials, ACTIMIS (NCT03803007) and GARDEN (NCT04659109), focused on bleeding events.In the ACTIMIS study, AIS patients were treated with SOC thrombolysis plus glenzocimab (1000 mg, 6-hour infusion) or placebo.In about 20% of case, patients were under ASA at arrival.In the GARDEN study, patients with severe COVID-19 received glenzocimab 1000 mg on three consecutive days; all were treated with heparin, mostly LMWH at therapeutic doses.Results: Non-Human Primate studies: In cynomolgus monkeys, the coadministration of alteplase/TNK and glenzocimab did not induce any bleeding, indicating the absence of pharmacological interaction and the safety of the combinations.Clinical Trials (1) ACTIMIS (Table 1): glenzocimab on top of alteplase did not increase the rate of bleeding events, even in patients exposed to ASA.In fact, glenzocimab administration was associated with reduced intracranial bleeding rates.(2) GARDEN: no death, no SUSAR and only 2 major bleedings, not treatment-related, occurred.Glenzocimab recurring treatment was not associated with an increase in bleeding events.