A Phase 1, Open-Label Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Single Intravenous Injection of Efanesoctocog Alfa in Adults with Type 2N or Type 3 von Willebrand Disease.

Background: Efanesoctocog alfa is a high-sustained factor VIII (FVIII) replacement therapy for haemophilia A. The D'D3 domain of efanesoctocog alfa overcomes the von Willebrand factor (VWF)-imposed half-life ceiling and may allow correction of reduced FVIII levels experienced by people with Type 2N or Type 3 von Willebrand disease (VWD).

Objectives: To assess the pharmacokinetics, safety, and tolerability of efanesoctocog alfa in Type 2N or Type 3 VWD.

Patients/methods: This was a Phase 1, open-label study of efanesoctocog alfa in adults with hereditary Type 2N or Type 3 VWD (NCT04770935). Participants received a single intravenous dose of efanesoctocog alfa (25 IU/kg). The primary endpoint was pharmacokinetic parameters as determined by non-compartmental analysis of efanesoctocog alfa FVIII activity using one-stage assay (OSA) and capture chromogenic (CCS) assay, the latter of which is more relevant in assessing FVIII levels from efanesoctocog alfa among people with VWD. Secondary endpoints included adverse events and FVIII inhibitor development.

Results: Six participants were assessed (Type 2N n=2; Type 3 n=4). One dose of efanesoctocog alfa 25 IU/kg maintained FVIII activity levels of >1 IU/dL up to 10 days post-dose. Mean baseline-corrected FVIII activity levels were maintained >40 IU/dL and >10 IU/dL up to 1 day and 4 days post-dose, respectively, per CCS assay. Mean (SD) t_1/2z was 49.0 (10.2) hours. Efanesoctocog alfa was well-tolerated. FVIII inhibitors or antidrug antibodies were not detected.

Conclusions: Efanesoctocog alfa is well-tolerated and maintains high FVIII activity levels for a prolonged period in patients with Type 2N or Type 3 VWD.