Efficacy, safety and bioequivalence of the human‐derived B‐domain‐deleted recombinant factor VIII TQG202 for prophylaxis in severe haemophilia A patients

• DOI: 10.1111/hae.14652
• Publication Date: 2022-08-23T03:30:27Z
• Authors: Yaming Xi; Chenghao Jin; Wei Liu; Hu Zhou; Zhen Wang; Rongfu Zhou; Shifeng Lou; Xielan Zhao; Fangping Chen; Peng Cheng; Zimin Sun; Haifei Jia; Lei Zhang
• Keywords: Adult; Male; Factor VIII; Adolescent; Hemorrhage; Original Articles; Hemophilia A; 16. Peace & justice; Hemostatics; 3. Good health; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Therapeutic Equivalency; Humans

AbstractIntroductionCurrent treatment of severe haemophilia A includes prophylaxis with factor VIII (FVIII) replacement. The supply of plasma‐derived FVIII is short in China.PurposeTo evaluate the efficacy and safety of a new B‐domain deleted (BDD) recombinant FVIII (TQG202) produced by human‐derived cells for prophylaxis in severe haemophilia A patients and compare the bioequivalence with Xyntha.MethodsThis multicentre, clinical trial consisted of an open‐label, randomized, two‐period cross‐over trial assessing single‐dose pharmacokinetics (PK), and a single‐arm clinical trial evaluating the efficacy and safety of 24 weeks of TQG202 prophylaxis, and repeated PK were assessed after prophylaxis phase. The single‐dose was 50 IU/kg in PK assessment, and the initial dose was 30 ± 5 IU/kg for prophylaxis. The primary endpoints of prophylaxis were the annualized bleeding rate (ABR) and the incremental recovery rate of the first administration. Adverse events (AEs) were recorded.ResultsTwenty‐six participants were enrolled in the PK assessment and 81 participants in the prophylaxis phase. Mean age was 25.9 ± 10.8 years and all participants were male. The results of PK assessment showed TQG202 is bioequivalent to Xyntha. The total ABR was 2.0 (95% CI: 1.2–2.9) in prophylaxis phase. The mean incremental recovery rate of the first administration was .027 (95% CI: .026–.028) (IU/ml)/(IU/kg). AEs occurred in 42 participants, with an incidence of 51.9%. One severe AE not related to TQG202 occurred. No participants developed FVIII inhibitors.ConclusionTQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice.