Vilchevska Kateryna, Balkan Can, Turea Valentin, Gurtchumelia Darejani, Loureiro Prezotti Alessandra Nunes, Oliveira de Oliveira Luciana Correa, Leon Julissa, Fosdal Mark, Mahlangu Johnny
National Specialized Children's Hospital OKHMATDYT, Center of Hemostasis Pathologies, Kyiv, Ukraine.
Ege University School of Medicine, Department of Child Health and Diseases, Kazimdirik Quarter, Bornova, İzmir, Turkey.
Res Pract Thromb Haemost. 2025 Feb 4;9(1):102655. doi: 10.1016/j.rpth.2024.102655. eCollection 2025 Jan.
Trenonacog alfa is a recombinant factor IX approved for adolescents and adults with hemophilia B.
The aim of this study was to assess the pharmacokinetics (PK), efficacy as prophylaxis, control of bleeding episodes, and safety of trenonacog alfa in previously treated participants aged <12 years with severe or moderately severe hemophilia B and no current or history of inhibitors.
The study had 3 phases: (1) PK evaluation after a single infusion of 75 ± 5 IU/kg, (2) treatment phase in which participants received trenonacog alfa prophylaxis 35 to 75 IU/kg for 50 exposure days, and (3) a continuation phase in which prophylaxis could be administered for ≥50 additional exposure days.
The PK of trenonacog alfa was comparable between adolescents and adults except for higher clearance, shorter mean residence time and elimination half-life, and lower incremental recovery. Prophylaxis resulted in a median annualized bleeding rate of 0.86 (mean = 2.34) for the combined treatment and continuation phases; 33.3% of participants had zero bleeds; and 83.7% of bleeds treated resolved with 1 or 2 infusions. One adverse event was possibly related to trenonacog alfa, a nonserious hypersensitivity reaction leading to early study termination. The efficacy and safety of trenonacog alfa for prophylaxis and bleeding treatment in previously treated pediatric participants were consistent with those reported for adults and adolescents. There appeared to be no clinically important differences between the results for participants aged <6 years and those aged 6 to <12 years.
Trenonacog alfa is a suitable option for the management of pediatric persons with hemophilia B.
曲诺那考因子α是一种已获批用于治疗青少年和成人B型血友病的重组因子IX。
本研究旨在评估曲诺那考因子α在既往接受过治疗、年龄<12岁、患有重度或中度重度B型血友病且目前或既往无抑制物史的参与者中的药代动力学（PK）、预防疗效、出血事件控制情况及安全性。
该研究有3个阶段：（1）单次输注75±5 IU/kg后的PK评估；（2）治疗阶段，参与者接受35至75 IU/kg的曲诺那考因子α预防治疗，持续50个暴露日；（3）延续阶段，预防治疗可再持续≥50个暴露日。
曲诺那考因子α在青少年和成人中的PK具有可比性，但清除率较高、平均驻留时间和消除半衰期较短以及增量回收率较低。在联合治疗阶段和延续阶段，预防治疗使年化出血率中位数为0.86（平均值=2.34）；33.3%的参与者无出血；83.7%接受治疗的出血事件在1或2次输注后得到缓解。1例不良事件可能与曲诺那考因子α有关，为导致研究提前终止的非严重过敏反应。曲诺那考因子α在既往接受过治疗的儿科参与者中用于预防和出血治疗的疗效及安全性与成人和青少年报告的一致。6岁以下参与者与6至<12岁参与者的结果之间似乎没有临床重要差异。
曲诺那考因子α是治疗儿童B型血友病的合适选择。
