关于抗狂犬病病毒单克隆抗体临床疗效评价的考虑

Cogitation on the clinical efficacy evaluation of anti-rabies virus monoclonal antibodies

狂犬病是我国传染病主要致死病因之一,病死率几乎100%。被动免疫是狂犬病暴露后预防的重要措施之一,目的是在第一针狂犬病疫苗注射后至机体产生足量抗体前的窗口期提供即时的免疫保护。抗狂犬病病毒单克隆抗体(简称狂犬病单抗)定位于狂犬病暴露后被动免疫,相对于现有被动免疫制剂具有成本降低、安全性提高的潜在优势。由于疾病和药物作用特点,狂犬病单抗临床试验设计和疗效评价存在诸多挑战。国家药品监督管理局2022年1月发布了《抗狂犬病病毒单克隆抗体新药临床试验技术指导原则》,为此类产品临床研发提供了具备科学性和可操作性的策略。本文通过分析狂犬病发病特点、被动免疫机制、已有被动免疫制剂的上市临床经验等,总结狂犬病单抗疗效评价中的关键问题,并对指导原则中推荐疗效指标的审评考虑进行说明。

Rabies is one of the main causes of death of infectious diseases in China, and the mortality is close to 100%. Passive immunization is an important measure in rabies postexposure prophylaxis, which purpose is to provide immediate immune protection in the window period of rabies vaccine. Anti-rabies virus monoclonal antibodies(rabies-mAbs) are a kind of drug for passive immunization after rabies exposure. Compared with the listed passive immune drugs, rabies-mAbs have the potential advantages of reducing the production costs and improving the safety. Due to the disease characteristics and drug mechanism, there are many challenges in the clinical trial design and efficacy evaluation of rabies-mAbs. The National Medical Products Administration of China released the clinical guidance for new rabies-mAbs products in January 2022, which provides a scientific and operable strategy for drug clinical development. This article will summarize the key problems in the efficacy evaluation of rabies-mAbs and explain the review considerations of recommended efficacy indicators in the guidance, via analyzing disease characteristics, passive immunization mechanism and listed drugs’ clinical experience.