Comparison of pharmacokinetics, pharmacodynamics, safety, and immunogenicity of teriparatide biosimilar with EU- and US-approved teriparatide reference products in healthy men and postmenopausal women.

Biosimilar teriparatide (INTG-8) was tested in a healthy population of males and postmenopausal females to assess pharmacokinetic bioequivalence to originator teriparatide comparator products. Primary pharmacokinetic comparison confirmed bioequivalence. Pharmacodynamics, safety, and tolerability were comparable to the originator products. INTG-8 was therefore confirmed to be biosimilar to originator products. INTRODUCTION: The purpose of this present study was to demonstrate pharmacokinetic (PK) equivalence of a biosimilar teriparatide (INTG8) to EU- and US-approved teriparatide reference products in healthy men and postmenopausal women. Secondary objectives included comparison of the pharmacodynamics (PD), safety, and tolerability. METHODS: One hundred and five subjects randomly (1:1:1) received single subcutaneous 20 µg injection of teriparatide biosimilar, EU- and US-teriparatide on 3 consecutive days in this assessor-blind, three-period, single-dose, crossover study. Maximum serum concentration (Cmax), area under the curve (AUC) from time zero to t (AUC0-t), and AUC from time zero extrapolated to infinity (AUC0-∞) were primary PK parameters, analyzed by non-compartmental methods. The secondary PD endpoints were maximum observed effect (Emax), area under the effect curve (AUE) from time zero to the last measurable concentration (AUE0-t), and time to maximum observed effect (Tmax) for total serum calcium levels. Safety, tolerability, and immunogenicity were also evaluated. This study was registered with ctri.nic.in/ (CTRI/2020/10/028627) on 26 October 2020. RESULTS: Baseline demographics were similar across the three-treatment sequence groups. The 90% confidence intervals (CI) for the geometric mean ratios (test:reference) of Cmax, AUC0-t, and AUC0-∞ were within the predefined bioequivalence criterion of 80.00% to 125.00%, which demonstrated PK equivalence of teriparatide biosimilar to EU- and US-teriparatide for all primary endpoints. The PD comparability was demonstrated by similar serum calcium levels. Study treatments were generally well tolerated and showed no meaningful differences in safety or immunogenicity profiles. There were no deaths, or serious AEs were reported during this study. CONCLUSION: The study demonstrated PK bioequivalence of teriparatide biosimilar to the EU- and US-teriparatide reference products with comparable PD, safety, and immunogenicity profiles.

A comparative multi-tiered immunogenicity assessment of biosimilar pegylated filgrastim: validation of methods for clinical assessment of INTP5.

BACKGROUND AND OBJECTIVE: Validated and highly sensitive assays are required for comparative assessment of immunogenicity of biosimilars. For INTP5, a biosimilar pegylated filgrastim, the immunogenicity assessment included tiers that allowed for assessment of antibodies against the PEG and the Filgrastim moieties for comparative clinical immunogenicity assessment. METHODS: Electrochemiluminescence immunoassay (ECLIA) was used for Screening, Specificity, and Titer assays for detecting anti-drug antibodies (ADAs) and cell-based method for neutralizing ADAs. The methods were validated to enable use of same methods irrespective of biosimilar or reference arms. RESULTS: The ADA and cell-based assay for neutralizing antibody detection were validated with a sensitivity capable of detecting binding Anti-Pegfilgrastim antibody at ~40 ng/mL and Neutralizing antibody at ~380 ng/mL and used for a comparative immunogenicity study. Of 194 subjects, 10 subjects had confirmed positive anti-drug-antibody in the biosimilar arm and 9 in the reference arm. None of the subjects were detected with neutralizing anti-drug antibodies. CONCLUSION: This work demonstrates the application of a rigorous approach toward validation of assays for immunogenicity studies for biosimilars. Highly sensitive, precise, and robust assays were used to conclude comparable low incidences of anti-drug antibodies in both biosimilar and innovator arms of the clinical study for Pegfilgrastim.