Establishing Analytical and Clinical Similarity Between HD201 and Trastuzumab

2020 Year in Review - Biosimilars —January 25, 2021

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Biosimilars

The totality of evidence generated from comparative systematic stepwise assessment of HD201 and trastuzumab reference in terms of analytical, pharmacodynamic, pharmacokinetic, and clinical similarity demonstrated the equivalence of HD201 to trastuzumab.

HD201 is a biosimilar candidate to trastuzumab indicated for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast and gastric cancers. At the 2020 American Society of Clinical Oncology Annual Meeting, an overview of the comparative systematic stepwise assessment of HD201 and trastuzumab reference in terms of analytical, pharmacodynamic, pharmacokinetic (PK), and clinical similarity was presented.

Bioanalytic similarity was demonstrated between HD201 and trastuzumab based on physiochemical and functional assessments. Physiochemical assessments consisted of evaluations of several quality attributes, including primary structure, higher-order structures, glycosylation, and purity/impurity by size, as well as charge variants; biological assays included those relating to mechanism of action. Analytical biosimilarity between the 2 products was demonstrated, with some minor changes in quality attributes that were not clinically meaningful. 

The program to demonstrate clinical similarity of HD201 to trastuzumab included 2 clinical studies. The first was the double-blind, randomized, parallel-group TROIKA-I study, which compared the PK and safety of HD201, EU-licensed trastuzumab, and US-approved trastuzumab in 101 healthy human subjects. The TROIKA-I study demonstrated the PK equivalence among the 3 cohorts, and that HD201 was safe and well-tolerated.

The second study (TROIKA) was a randomized, double-blind, parallel-group phase 3 trial that compared the efficacy of HD201 with EU-trastuzumab in 251 patients with HER2-positive early breast cancer. Eligible patients received HD201 or EU-trastuzumab in combination with chemotherapy as neoadjuvant therapy followed by HD201 or EU-trastuzumab alone in the adjuvant phase. The primary end point was total pathologic complete response (tpCR). In the neoadjuvant phase, patients in the HD201 group achieved a tpCR of 46.6%, whereas those in the trastuzumab group achieved a tpCR of 46.2%, with the 95% confidence interval being within the prespecified equivalence margins (–15%-15%), establishing equivalence between the 2 groups. Safety and PK profiles were comparable between the 2 groups.

The totality of evidence generated from the comparative exercise among HD201, EU-licensed trastuzumab, and US-approved trastuzumab demonstrated the equivalence of HD201 to trastuzumab.

Reference
Hii J, et al. ASCO 2020. Abstract 579.

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Last modified: January 25, 2021

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