Center for Health Regulatory Policies, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy.
Eur J Clin Pharmacol. 2020 Apr;76(4):557-566. doi: 10.1007/s00228-019-02805-y. Epub 2020 Jan 2.
To review the marketing authorization of biosimilars and provide a critical analysis of the pivotal trials supporting their approval by the European Medicines Agency (EMA).
EMA website to identify the biosimilars approved up to July 2019 and the European Public Assessment Report for information on pivotal trial design, duration, intervention and control, primary outcome, data on immunogenicity, and comparability margins.
The EMA has approved 55 biosimilars (62% in 2017-2019) of 16 biologic products, used in several clinical indications. Some biosimilars were licensed as multiple products, with different commercial names, by the same or different companies. The comparability exercise and subsequent approval of 49/55 (89%) biosimilars were based on one or more pivotal phase III trials testing their clinical efficacy. In all, biosimilars were approved on the basis of 55 trials, mostly phase III (42/55, 76%) assessing clinical efficacy; these were mainly equivalence trials (31/55, 56%). The pivotal phase III trials assessed surrogate measures of clinical effect, and 71% reported immunogenicity data.
Analysis of the approval of biosimilars in Europe depicts a complex and heterogeneous scenario. The requirement for showing similarity in terms of clinical efficacy and safety provides a robust demonstration of comparable clinical outcomes but lays a burden on biosimilar manufacturers and may delay the introduction of the drugs. The development, licensing, and monitoring of biosimilars would benefit from new strategies to accelerate access to these drugs while reducing uncertainties about their use in practice.
审查生物类似药的上市许可，并对支持其获得欧洲药品管理局（EMA）批准的关键性试验进行批判性分析。
通过 EMA 网站，确定截至 2019 年 7 月批准的生物类似药，并查阅欧洲公共评估报告，以获取关于关键性试验设计、持续时间、干预和对照、主要结局、免疫原性数据以及可比性边界的信息。
EMA 已批准 16 种生物制品中 55 种（2017-2019 年占 62%）生物类似药，用于多种临床适应证。一些生物类似药由同一家或不同公司以不同商品名作为多种产品获得许可。49/55（89%）种生物类似药的可比性研究和随后的批准是基于一项或多项测试其临床疗效的关键性 III 期试验。总之，基于 55 项试验（其中 42 项为 III 期，占 76%）批准了生物类似药，主要是评估临床疗效的等效性试验（31 项，占 56%）。关键性 III 期试验评估了临床效果的替代指标，71%的试验报告了免疫原性数据。
对欧洲生物类似药批准情况的分析描绘了一个复杂而多样化的场景。在临床疗效和安全性方面表现出相似性的要求提供了可比临床结果的有力证明，但给生物类似药制造商带来了负担，并可能延迟药物的推出。生物类似药的开发、许可和监测将受益于新的策略，以加速这些药物的获得，同时减少对其实际应用的不确定性。
