Evaluation of the safety, pharmacokinetics, and efficacy of recombinant factor VIII fc fusion protein in Japanese subjects with severe haemophilia A: analysis from the A-LONG study

: Introduction: Recombinant factor VIII Fc fusion protein (rFVIIIFc) was safe and efficacious for control and prevention of bleeding in the multinational Phase 3 A-LONG study of previously treated males aged ≥ 12 years with severe haemophilia A. This post hoc subgroup analysis evaluated safety, efficacy, and pharmacokinetics of rFVIIIFc in Japanese subjects (n = 14). Methods: Subjects received individualised prophylaxis (starting 25 IU/kg rFVIIIFc on Day 1, 50 IU/kg on Day 4; then 25–65 IU/kg every 3–5 days), weekly prophylaxis (65 IU/kg rFVIIIFc once weekly), or episodic treatment (10–50 IU/kg rFVIIIFc as needed). Primary endpoints were annualised bleeding rates (ABRs) and safety. Results: Most pharmacokinetic parameters were comparable with rFVIIIFc treatment between Japanese and non-Japanese subjects. Incremental recovery was lower in Japanese (1.7 [IU/dL]/[IU/kg]) versus non-Japanese subjects (2.2 [IU/ dL]/[IU/kg]), likely related to lower average BMI and body weight for Japanese subjects. Median ABRs for Japanese subjects in the individualised prophylaxis, weekly prophylaxis, and episodic arms were 3.56, 4.34, and 25.06, respectively. Most bleeding episodes (89.5%) resolved with 1 rFVIIIFc injection. No inhibitors were reported; safety findings were comparable to non-Japanese subjects. Conclusion: rFVIIIFc was safe and efficacious for control and prevention of bleeding in Japanese subjects, with outcomes comparable to non-Japanese subjects.