COMPARISON OF PHARMACOKINETIC, PHARMACODYNAMIC AND SAFETY OF A TERIPARATIDE BIOSIMILAR AND REFERENCE TERIPARATIDE

Background: Intas is developing a biosimilar teriparatide. This teriparatide biosimilar has shown similarity to European Union approved teriparatide (EU teriparatide) and United States approved teriparatide (US-teriparatide) in analytical (structural and functional assays) and animal studies1. Objectives: To primarily asses pharmacokinetic (PK) equivalence and to compare pharmacodynamic (PD) and safety profiles of teriparatide biosimilar against EU- and US-teriparatide in healthy men and postmenopausal women with potentially similar in-clinic real-life user profiles. Methods: In this assessor-blind, three-period study, 105 subjects were randomized (1:1:1) to receive single subcutaneous 20μg dose each of teriparatide biosimilar, EU-teriparatide, and US-teriparatide in a crossover manner on 3 consecutive days. The primary PK endpoints were area under the curve (AUC) from time zero to t (AUC0-t), AUC from time zero to infinity (AUC0-∞), and maximum concentration (Cmax). Secondary endpoints were total serum calcium level as a pharmacodynamic marker and safety. Results: The mean age of 48 men was 38.4 years and 57 women was 43.9 years. Mean serum teriparatide concentrations were similar for teriparatide biosimilar, EU- and US-teriparatide (Figure 1). The 90% confidence intervals (CI) of the geometric least square mean ratios (GMR) of Cmax, AUC0-t and AUC0-∞ of teriparatide biosimilar relative to EU- and US-teriparatide were within the predefined acceptance range of 80.00% to 125.00% (Table 1). The baseline-adjusted and non-adjusted corrected total serum calcium levels were similar (Table 2). A total of 42 adverse events (AE) were reported by 31 (29.52%) subjects (9 subjects, teriparatide biosimilar; 14 subjects, EU-teriparatide; 13 subjects, US-teriparatide), with headache and pain in extremity being the most common AEs. No death or serious AEs were reported. Conclusion: This study showed PK equivalence as well as similar PD and safety profiles between teriparatide biosimilar, EU-teriparatide and US-teriparatide in healthy subjects. References: [1]Data on file Disclosure of Interests: Inderjeet Singh Employee of: Intas Pharmaceuticals Limited, Anshul Attrey Employee of: Lambda Therapeutics Research Limited, Ronak Patel Employee of: Lambda Therapeutics Research Limited, Sridevi Khambhampaty Employee of: Intas Pharmaceuticals Limited, Vinu Jose Employee of: Intas Pharmaceuticals Limited