Nonclinical Similarity of the Biosimilar Candidate ABP 938 with Aflibercept Reference Product.

IF 2.6 3区医学 Q2 OPHTHALMOLOGY

Ophthalmology and Therapy Pub Date : 2024-11-06 DOI:10.1007/s40123-024-01043-5

Neungseon Seo, Scott Kuhns, Dina A Andrews, Alexander Colbert, Vincent Chow, Jennifer Liu

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引用次数: 0

Abstract

Introduction: ABP 938 is being developed as a biosimilar to Eylea^® (aflibercept reference product [RP]), an anti-vascular endothelial growth factor (VEGF) drug used in the management of retinal diseases. Previously, a comparative analytical similarity assessment demonstrated that ABP 938 and aflibercept RP have the same amino acid sequence and exhibit similar higher-order structure and biological activity. The nonclinical studies described here were designed to assess the in vitro pharmacology and the in vivo pharmacokinetics (PK), toxicokinetics (TK), and safety profiles of ABP 938 compared to aflibercept RP.

Methods: In vitro target-binding kinetics and affinity for VEGF-A and placental growth factor (PIGF) isoforms were evaluated using surface plasmon resonance (SPR). Effector functions were assessed by cell-based assays. PK was evaluated in a nonterminal intravitreal (IVT) ocular distribution study in rabbits. Safety was assessed in a 1-month IVT study in cynomolgus monkeys.

Results: SPR results demonstrated that ABP 938 is similar to aflibercept RP in binding kinetics and affinity for VEGF-A₁₁₁, VEGF-A₁₂₁, VEGF-A₁₆₅, VEGF-A₁₈₉, PlGF-1, and PlGF-2 isoforms. No antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity was observed with ABP 938 and aflibercept RP. Results from the nonterminal ocular distribution study in rabbits indicated that there were no meaningful differences in the distribution kinetics between intravitreally injected ABP 938 and aflibercept RP. Additionally, there was no evidence of ocular or systemic toxicity associated with IVT administration of ABP 938 in a repeat-dose, 1-month toxicology study in cynomolgus monkeys; toxicokinetic and toxicology profiles were similar to aflibercept RP.

Conclusions: This integrated assessment of results from the in vitro pharmacology assessment and in vivo PK and TK/toxicology profiles formed the nonclinical portion of the totality of evidence demonstrating ABP 938 is a biosimilar to aflibercept RP.

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生物仿制药候选药物 ABP 938 与 Aflibercept 参考产品的非临床相似性。

简介：ABP 938是Eylea®（aflibercept参比产品[RP]）的生物仿制药，Eylea®是一种用于治疗视网膜疾病的抗血管内皮生长因子（VEGF）药物。此前的分析相似性比较评估表明，ABP 938和阿弗利百普RP具有相同的氨基酸序列，并表现出相似的高阶结构和生物活性。本文所述的非临床研究旨在评估ABP 938与aflibercept RP相比的体外药理学和体内药代动力学（PK）、毒代动力学（TK）和安全性概况：方法：利用表面等离子体共振（SPR）评估了体外靶向结合动力学以及与血管内皮生长因子-A和胎盘生长因子（PIGF）同种异构体的亲和力。通过基于细胞的试验评估了其效应功能。在兔子体内进行的非终末静脉注射（IVT）眼部分布研究对 PK 进行了评估。在犬科猴体内进行了为期 1 个月的静脉注射研究，对其安全性进行了评估：SPR结果表明，ABP 938与阿夫利拜特RP的结合动力学和对血管内皮生长因子-A111、血管内皮生长因子-A121、血管内皮生长因子-A165、血管内皮生长因子-A189、PlGF-1和PlGF-2同工酶的亲和力相似。ABP 938和aflibercept RP未观察到抗体依赖性细胞毒性、抗体依赖性细胞吞噬或补体依赖性细胞毒性。兔子非终端眼部分布研究结果表明，玻璃体内注射ABP 938和aflibercept RP的分布动力学没有明显差异。此外，在对眼镜猴进行的为期1个月的重复剂量毒理学研究中，没有证据表明静脉注射ABP 938会引起眼部或全身毒性；毒物动力学和毒理学特征与aflibercept RP相似：对体外药理学评估结果和体内PK、TK/毒理学特征的综合评估构成了证明ABP 938是aflibercept RP生物类似药的全部证据的非临床部分。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ophthalmology and Therapy OPHTHALMOLOGY-

CiteScore

4.20

自引率

3.00%

发文量

157

审稿时长

6 weeks

期刊介绍： Aims and Scope Ophthalmology and Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from preclinical, clinical (all phases), observational, real-world, and health outcomes research around the use of ophthalmological therapies, devices, and surgical techniques. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Ophthalmology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of ophthalmic therapies. Open Access All articles published by Ophthalmology and Therapy are open access. 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