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 (F)VIII replacement therapy for hemophilia A. The D'D3 domain of efanesoctocog alfa overcomes the von Willebrand factor-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

This study aimed to assess the pharmacokinetics, safety, and tolerability of efanesoctocog alfa in type 2N or type 3 VWD.

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 end point was pharmacokinetic parameters as determined by noncompartmental analysis of efanesoctocog alfa FVIII activity using one-stage assay and capture chromogenic assay, the latter of which is more relevant in assessing FVIII levels from efanesoctocog alfa among people with VWD. Secondary end points 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 of 25 IU/kg maintained FVIII activity levels of >1 IU/dL up to 10 days postdose. Mean baseline-corrected FVIII activity levels were maintained at >40 and >10 IU/dL up to 1 day and 4 days postdose, respectively, per capture chromogenic assay. Mean (standard deviation) t was 49.0 (10.2) hours. Efanesoctocog alfa was well tolerated. FVIII inhibitors or antidrug antibodies were not detected.

CONCLUSION

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