The efficacy, safety, and pharmacokinetics of N8-GP in previously treated Chinese patients with haemophilia A: results from the phase 3b pathfinder10 study.

INTRODUCTION

N8-GP (turoctocog alfa pegol) is a recombinant, glycoPEGylated, extended half-life FVIII replacement product approved for treatment of haemophilia A (HA).

AIM: The pathfinder10 (NCT05082116) multicentre, open-label, nonrandomised, single-arm phase 3b trial investigated N8-GP efficacy, safety, and pharmacokinetics in previously treated Chinese patients.

METHODS

Patients (≥12 years) with severe HA, FVIII activity <1%, ≥150 exposure days to FVIII products, and no FVIII inhibitors (≥0.6 BU) or history were enrolled and received 50 IU/kg N8-GP prophylaxis every four days for ≥28 weeks. Bleeding episodes were treated with 20-75 IU/kg N8-GP. The primary endpoint was the number of treatment-requiring bleeding episodes (spontaneous, traumatic). Secondary endpoints included haemostatic effect, inhibitor rate, FVIII trough activity, and pharmacokinetics.

RESULTS

Thirty-six patients completed the trial. During 12 months pretrial, 17 (47%) patients received a mixture of episodic and prophylactic regimens, and 1 (3%) episodic treatment only, and the mean (SD) and median number of bleeding episodes during prophylaxis were 11.0 (11.1) and 5.0. During N8-GP prophylaxis, mean (95% CI) and median ABR were 2.55 (1.24; 5.23) and 0.00. No bleeds were reported in 25/36 patients (69.4%). The haemostatic success rate for bleed treatment was 94.8% (73.2; 99.2). Most bleeds (49/52; 94.2%) were treated with ≤2 injections; 42/52 (80.8%) needed 1 injection. Mean FVIII activity trough level (predose) was 3.3 IU/dl (2.6; 4.3), mean postdose recovery 126.1 IU/dl (116.9; 136.0), N8-GP terminal half-life 19.9 h (18.6, 21.2), 30 min IR 2.28 (IU/dl)/(IU/kg) (2.05, 2.52), and AUC (0-96 h) (single dose) 31.8 h*(IU/ml) (28.9; 34.9). No inhibitors or safety concerns were identified.

CONCLUSION

N8-GP appeared safe and efficacious in previously treated Chinese patients with severe HA.