FRONTIER5: Safety and patient experience of a direct switch from emicizumab to denecimig (Mim8) in patients with haemophilia A with or without inhibitors.

Abstract

Background: Denecimig (Mim8) is an activated factor VIII mimetic, fully human, bispecific IgG4 antibody in development for subcutaneous prophylaxis in patients with haemophilia A (HA) with/without inhibitors.

Objective: To evaluate the safety and patient experience of a direct switch from emicizumab to denecimig prophylaxis without a washout period or loading dose.

Methods: FRONTIER5 (NCT05878938) was a 26-week, single-arm, open-label, phase 3b study in patients aged ≥12 years with HA with or without factor VIII inhibitors. Patients transitioned directly from emicizumab to denecimig maintenance doses administered subcutaneously once-every week, once-every-two-weeks, or once-every-month by a pen-injector. The primary endpoint was the number of treatment-emergent adverse events (TEAEs); secondary and exploratory endpoints included thrombin generation, and patient-reported pen-injector experience, treatment burden, joint pain, and physical activity.

Results: All 61 enrolled patients completed the study. TEAEs occurred in 70.5% of patients (3.48 per patient-year of exposure). Most TEAEs were mild or moderate in severity and not treatment-related. No thromboembolic events, hypersensitivity reactions, or clinical evidence of neutralising anti-denecimig antibodies were observed. Injection-site reactions were observed in 15/990 (1.5%) injections. Thrombin generation with denecimig increased into the normal reference range by week 1, without exaggerated haemostatic response. Without a loading dose, denecimig reached steady-state plasma concentrations by week 16. Most participants (98.3%) rated the denecimig pen-injector as 'easy' or 'very easy' to use.

Conclusion: The direct switch from emicizumab to denecimig without a washout period was well tolerated in adolescents and adults with HA with or without inhibitors. No new safety concerns were observed.