Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
Division of Bioequivalence I, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD. United States.
CNS Neurol Disord Drug Targets. 2017;16(6):714-723. doi: 10.2174/1871527316666170223162747.
In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone.
This article will provide an overview of the methods used to establish the biological and immunological equivalence of the two glatiramer acetate products, including methods evaluating antigenpresenting cell (APC) biology, T-cell biology, and other immunomodulatory effects.
In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, APC biology, T-cell biology, and B-cell biology) modulated by glatiramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described. The following were observed when comparing Glatopa and Copaxone in these experiments: equivalent delays in symptom onset and reductions in "disease" intensity in experimental autoimmune encephalomyelitis; equivalent dose-dependent increases in Glatopa- and Copaxone- induced monokine-induced interferon-gamma release from THP-1 cells; a shift to a T helper 2 phenotype resulting in the secretion of interleukin (IL)-4 and downregulation of IL-17 release; no differences in immunogenicity and the presence of equivalent "immunofingerprints" between both versions of glatiramer acetate; and no stimulation of histamine release with either glatiramer acetate in basophilic leukemia 2H3 cell lines.
In summary, this comprehensive approach across different biological and immunological pathways modulated by glatiramer acetate consistently supported the biological and immunological equivalence of Glatopa and Copaxone.
2015 年 4 月，美国食品和药物管理局批准了第一种通用型那他珠单抗，即 Glatopa®（M356），可完全替代 Copaxone®20mg/mL 用于多发性硬化症（MS）的复发形式。这一批准是通过简化新药申请实现的，该申请证明了与 Copaxone 的等效性。
本文将概述用于确定两种那他珠单抗产品在生物学和免疫学上等效性的方法，包括评估抗原呈递细胞（APC）生物学、T 细胞生物学和其他免疫调节作用的方法。
在四个生物学过程（聚集物生物学、APC 生物学、T 细胞生物学和 B 细胞生物学）中进行的、来自多个冗余正交实验的体内和体外实验，确定了 Glatopa 和 Copaxone 的生物学和免疫学等效性，并对其进行了描述。在这些实验中比较 Glatopa 和 Copaxone 时，观察到以下结果：实验性自身免疫性脑脊髓炎中症状出现的延迟和“疾病”强度的降低相当；Glatopa 和 Copaxone 诱导的 THP-1 细胞中单核细胞诱导干扰素-γ释放的剂量依赖性增加相当；向 T 辅助 2 表型的转变导致白细胞介素（IL）-4 的分泌增加和 IL-17 释放的下调；两种那他珠单抗版本之间无免疫原性差异且存在等效的“免疫指纹”；两种那他珠单抗在嗜碱性白血病 2H3 细胞系中均不刺激组胺释放。
总之，这种综合方法涵盖了那他珠单抗调节的不同生物学和免疫学途径，一致支持 Glatopa 和 Copaxone 的生物学和免疫学等效性。
