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    Poster Networking

    Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies

    Poster Networking Session

    PB0364 - Glycoprotein VI-targeted antiplatelet therapy with glenzocimab is safe in patients exposed to current antithrombotic and fibrinolytic drugs.

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    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 non-observable 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 co-administration 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 (Table1): 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.

    Conclusion(s): Glenzocimab does not increase the bleeding risk, even in combination with antithrombotic and fibrinolytic agents. Overall, glenzocimab meets safety requirements in AIS treatment. Yet, administration of glenzocimab to patients exposed to ADP receptor antagonists deserves further study.