Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Therapeutic Biologics Program, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Pharmacol Ther. 2023 Jan;113(1):55-61. doi: 10.1002/cpt.2761. Epub 2022 Nov 2.
A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from a US Food and Drug Administration (FDA)-approved reference product. The development and approval of biosimilars is critical to enhancing the availability of safe, effective, and affordable treatment options for patients. Utilization of pharmacodynamic (PD) biomarkers can help streamline biosimilar development programs as the current process can be costly and time-consuming. Whereas PD biomarkers have not been prominently used across biosimilar approvals to date, moving forward, there is ample opportunity to increase the use of PD biomarkers in biosimilar development programs in place of comparative clinical studies with efficacy end point(s). This includes utilizing PD biomarkers that were not used as surrogate end points in approval of reference products. This mini-review summarizes how PD biomarkers have been used in biosimilar development programs to date and then discusses evidentiary considerations for PD biomarkers. In addition, study design considerations for clinical pharmacokinetic and PD assessment of proposed biosimilars are discussed. Finally, the FDA's applied regulatory science activities related to PD biomarkers for biosimilars conducted in support of the FDA's Biosimilars Action Plan are reviewed. This included conducting three clinical studies to address information gaps about PD biomarkers for biosimilars and inform general methodological best practices. In summary, enhancing our understanding of key evidentiary considerations and optimal study designs for incorporating PD biomarkers in the evaluation of proposed biosimilars can help bring more treatment options to patients faster.
生物类似药是一种与美国食品和药物管理局 (FDA) 批准的参比产品高度相似且无临床意义差异的生物制品。开发和批准生物类似药对于增强患者获得安全、有效和负担得起的治疗选择的可及性至关重要。利用药效学 (PD) 生物标志物可以帮助简化生物类似药开发项目，因为目前的过程既昂贵又耗时。虽然 PD 生物标志物在迄今为止的生物类似药批准中并未得到广泛应用，但未来有充分的机会增加 PD 生物标志物在生物类似药开发项目中的使用，以替代具有疗效终点的比较临床研究。这包括利用在批准参比产品时未用作替代终点的 PD 生物标志物。本综述总结了迄今为止 PD 生物标志物在生物类似药开发项目中的应用情况，然后讨论了 PD 生物标志物的证据考虑因素。此外，还讨论了用于评估拟议生物类似药的临床药代动力学和 PD 评估的研究设计考虑因素。最后，审查了 FDA 为支持 FDA 生物类似药行动计划而开展的与生物类似药 PD 生物标志物相关的应用监管科学活动。这包括开展三项临床研究，以解决关于生物类似药 PD 生物标志物的信息空白，并为一般方法学最佳实践提供信息。总之，增强我们对纳入 PD 生物标志物评估拟议生物类似药的关键证据考虑因素和最佳研究设计的理解，可以帮助更快地为患者带来更多的治疗选择。
