Institute Krems Bioanalytics, IMC University of Applied Sciences Krems, Krems, Austria.
Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Blood Adv. 2024 Jun 11;8(11):2726-2739. doi: 10.1182/bloodadvances.2023011780.
Rurioctocog alfa pegol is an extended-half-life full-length recombinant factor VIII (FVIII) bound to 20-kDa polyethylene glycol (PEG) that has been shown to be well tolerated and efficacious in the treatment and prevention of bleeding events in previously treated patients with severe hemophilia A. Here, we present a comprehensive analysis of immunogenicity data collected during 6 clinical studies of rurioctocog alfa pegol, including a total of 360 unique previously treated patients with severe hemophilia A. The analysis included treatment-emerging FVIII-neutralizing antibodies (FVIII inhibitors); preexisting and treatment-emerging antibodies binding to FVIII, PEG-FVIII, or PEG; and treatment-emerging antibodies binding to Chinese hamster ovary host cell proteins. Moreover, the potential association between the presence of these binding antibodies and adverse events (AEs) observed in patients was investigated, and the potential impact of these antibodies on the incremental recovery of rurioctocog alfa pegol in patients was analyzed. Overall, the data indicate that rurioctocog alfa pegol is not associated with any unexpected immunogenicity characteristics. Of 360 patients, 1 patient developed a transient FVIII inhibitor with a titer of 0.6 Bethesda units per mL, which was not associated with any serious AEs. Antibodies binding to FVIII, PEG-FVIII, or PEG were not detected at the time when the inhibitor was present. Moreover, 54 of 360 patients either entered the clinical studies with preexisting binding antibodies or developed these antibodies after exposure to rurioctocog alfa pegol. These antibodies were transient in most patients and did not show any causal relationship to either AEs or spontaneous bleeding episodes.
聚乙二醇结合重组因子 VIII（FVIII）长效制剂（rurioctocog alfa pegol）是一种全长重组 FVIII，通过 20kDa 聚乙二醇（PEG）结合，在既往接受过治疗的重度 A 型血友病患者中，其治疗和预防出血事件的疗效和安全性已得到证实。在此，我们对 6 项 rurioctocog alfa pegol 临床研究的免疫原性数据进行了全面分析，这些研究共纳入了 360 例既往接受过治疗的重度 A 型血友病患者。分析内容包括治疗中出现的 FVIII 中和抗体（FVIII 抑制剂）、治疗前和治疗中出现的与 FVIII、PEG-FVIII 或 PEG 结合的抗体，以及治疗中出现的与中国仓鼠卵巢宿主细胞蛋白结合的抗体。此外，还研究了这些结合抗体的存在与患者观察到的不良事件（AE）之间的潜在关联，并分析了这些抗体对 rurioctocog alfa pegol 患者增量恢复的潜在影响。总体而言，数据表明 rurioctocog alfa pegol 无任何意外的免疫原性特征。360 例患者中有 1 例出现了一过性 FVIII 抑制剂，其效价为 0.6 个 Bethesda 单位/毫升，且与任何严重 AE 无关。当抑制剂存在时，未检测到与 FVIII、PEG-FVIII 或 PEG 结合的抗体。此外，360 例患者中有 54 例在入组临床研究时就存在预存结合抗体，或在接触 rurioctocog alfa pegol 后产生了这些抗体。这些抗体在大多数患者中是一过性的，与 AE 或自发性出血事件之间没有任何因果关系。
