A Phase I, Randomized, Single-Dose Study to Evaluate the Biosimilarity of HOT-3010 to Adalimumab Among Healthy Chinese Male Subjects.

Hong Zhang,Yongmin Yang,Hong Chen,Xiaojiao Li,Xiaoxue Zhu,Yanhua Ding,Min Wu,Jingjing Wang,Yue Hu,Xiangyang Zhu,Haijing Wei,Cuiyun Li,Jingrui Liu

doi:10.3389/fphar.2021.646171

Abstract

Objective: This study explored the bioequivalence of a proposed biosimilar HOT-3010 vs. its reference product (adalimumab) among healthy Chinese male subjects. The study also investigated the tolerance, immunogenicity, and pharmacokinetics (PK). Methods: A randomized, double-blind, two-arm, parallel study was performed to examine the bioequivalence of HOT-3010 (40 mg) with that of adalimumab (Humira®, AbbVie) as a reference drug. The study subjects were followed up for 71 days. Results: PK properties exhibited by HOT-3010 (N = 66) and adalimumab (N = 68) groups were similar. The 90% confidence intervals of the ratios for C max, AUC0-t, and AUC0∞ were observed to be in the range 80–125% on comparing the two groups. For anti-drug antibodies (ADA), the number of subjects found to be positive in the HOT-3010 group and adalimumab group were 29 (43.94%) and 32 (47.06%), whereas 27 (40.91%) and 27 (39.71%) subjects were found to be positive for NAb, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were recorded in 32 subjects each in both the groups, respectively. Conclusion: The PK characteristics and immunogenicity exhibited by HOT-3010 were similar to that of the reference product, adalimumab. The safety profiles were similar in both the treatment groups with mild-moderate adverse effects.

Highlights

Derived from living cells, biological products are different large and complex molecules
A step-by-step approach for the development of biosimilars has been suggested by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and National Medical Products Administration (NMPA) (European Medicines Agency, 2015)
Two of the 136 subjects enrolled in the HOT-3010 group pulled out of the study owing to increased blood pressure ahead of the dose administration

Summary

Introduction

Derived from living cells, biological products are different large and complex molecules. Owing to biologics’ molecular complexity and multifaceted production process, biosimilars are characterized differently from traditional small molecules (European Medicines Agency, 2015; US Food and Drug Administration, 2015; World Health Organization, 2015). Biologic therapies such as monoclonal antibodies are expensive and limit access worldwide (Zelenetz and Becker, 2016), despite. The biological functional similarity was first assessed, followed by pharmacokinetic (PK) and pharmacodynamic (PD) properties, and at last, clinical similarity, including efficacy, safety, and immunogenicity was assessed, through the approved dose and pathway as that of the reference product (European Medicines Agency, 2015; US Food and Drug Administration, 2015; World Health Organization, 2015)

Methods

Results

Discussion

Conclusion