美国Versiti血液研究所Lynn Malec团队研究了Efanesoctocog Alfa预防儿童严重血友病A的效果与安全性。2024年7月18日，《新英格兰医学杂志》发表了这一成果。

与先前治疗过的12岁或以上严重血友病A患者的研究前因子VIII预防相比，每周一次的Efanesoctocog Alfa可提供高持续的因子VIII活性，并具有更好的出血预防效果。关于Efanesoctocog Alfa治疗12岁以下严重血友病A儿童结局的数据有限。

研究组进行了一项3期开放标签研究，招募之前接受过治疗的12岁以下严重血友病A患者。患者接受了为期52周的每周一次Efanesoctocog Alfa（每公斤体重50 IU）预防。主要终点是出现因子VIII抑制剂（针对因子VIII的中和抗体）。次要终点包括治疗出血事件的年化率、出血治疗、安全性和药代动力学。

研究组共招募了74名男性患者（38名年龄<6岁，36名年龄在6至<12岁之间）。均未发现因子VIII抑制剂。大多数不良事件并不严重。没有报告研究者评估为与Efanesoctocog Alfa有关的严重不良事件。在根据方案治疗的73名患者中，中位数和基于模型的平均年出血率分别为0.00（四分位数间距，0.00至1.02）和0.61（95%置信区间，0.42至0.90）。47名患者（64%）无治疗出血事件，65名患者（88%）无自发性出血事件，61名患者（82%）无关节出血事件。43例出血事件中，共有41例（95%）通过一次注射Efanesoctocog Alfa得到缓解。给药后3天，稳态下的平均因子VIII活性超过每分升40 IU，近7天超过每分升10 IU。几何平均终末半衰期为40.0小时。

研究结果表明，在患有严重血友病A的儿童中，每周一次的Efanesoctocog Alfa预防措施在给药后3天内提供了正常至接近正常范围内的高持续因子VIII活性（>40IU/分升），并在近7天内提供超过10IU/分升的活性，从而有效地预防了出血。Efanesoctocog Alfa主要与非严重不良事件有关。

附：英文原文

Title: Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A

Author: Lynn Malec, Flora Peyvandi, Anthony K.C. Chan, Christoph Knigs, Bulent Zulfikar, Huixing Yuan, Mindy Simpson, Maria Teresa álvarez Román, Manuel Carcao, Janice M. Staber, Amy L. Dunn, Sheng-Chieh Chou, Roseline d’Oiron, Manuela Albisetti, Marek Demissie, Elena Santagostino, Abhimanyu Yarramaneni, Nancy Wong, Lydia Abad-Franch, Sriya Gunawardena, Karin Fijnvandraat

Issue&Volume: 2024-07-18

Abstract:

BACKGROUND

Once-weekly efanesoctocog alfa provides high sustained factor VIII activity with superior bleeding prevention as compared with prestudy factor VIII prophylaxis in previously treated patients 12 years of age or older with severe hemophilia A. Data on outcomes of efanesoctocog alfa treatment in children younger than 12 years of age with severe hemophilia A are limited.

METHODS

We conducted a phase 3, open-label study involving previously treated patients younger than 12 years of age with severe hemophilia A. Patients received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. The primary end point was the occurrence of factor VIII inhibitors (neutralizing antibodies against factor VIII). Secondary end points included annualized rates of treated bleeding episodes, bleeding treatment, safety, and pharmacokinetics.

RESULTS

A total of 74 male patients were enrolled (38 with an age of <6 years and 36 with an age of 6 to <12 years). No factor VIII inhibitors developed. Most adverse events were nonserious. No serious adverse events that were assessed by the investigator as being related to efanesoctocog alfa were reported. In the 73 patients treated according to the protocol, the median and model-based mean annualized bleeding rates were 0.00 (interquartile range, 0.00 to 1.02) and 0.61 (95% confidence interval, 0.42 to 0.90), respectively. A total of 47 patients (64%) had no treated bleeding episodes, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints. A total of 41 of 43 bleeding episodes (95%) resolved with one injection of efanesoctocog alfa. Mean factor VIII activity at steady state was more than 40 IU per deciliter for 3 days and more than 10 IU per deciliter for almost 7 days after dose administration. The geometric mean terminal half-life was 40.0 hours.

CONCLUSIONS

In children with severe hemophilia A, once-weekly prophylaxis with efanesoctocog alfa provided high sustained factor VIII activity in the normal to near-normal range (>40 IU per deciliter) for 3 days and more than 10 IU per deciliter for almost 7 days after administration, leading to effective bleeding prevention. Efanesoctocog alfa was associated with mainly nonserious adverse events.

DOI: NJ202407183910309

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2312611