SAT0451 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 studies 1 . 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 (AUC 0-t ), AUC from time zero to infinity (AUC 0-∞ ), and maximum concentration (C max ). 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 C max , AUC 0-t and AUC 0-∞ 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. Table 1. Summary of Statistical Analysis of Pharmacokinetic Parameters of Teriparatide Parameters N GLSM N GLSM Ratio (T/R1) % 90% Confidence Interval Teriparatide Biosimilar (T ) EU-Teriparatide (R1 ) lnC max (pg/mL) 104 99.314 104 99.229 100.1 95.50 - 104.89 lnAUC 0-t (pg.h/mL) 103 130.402 103 129.067 101.0 96.37 - 105.93 lnAUC 0-∞ (pg.h/mL) 103 150.589 103 144.887 103.9 99.19 - 108.90 Teriparatide Biosimilar (T ) US-Teriparatide (R2 ) Ratio (T/R2) % lnC max (pg/mL) 104 99.255 104 96.397 103.0 98.74 - 107.37 lnAUC 0-t (pg.h/mL) 102 131.212 102 126.837 103.4 98.90 - 108.21 lnAUC 0-∞ (pg.h/mL) 102 150.564 102 143.860 104.7 99.88 - 109.67 GLSM: Geometric least squares mean; N: Number of subjects. Table 2. Summary of Corrected Total Serum Calcium Levels after Administration of Teriparatide Parameter Teriparatide Biosimilar EU-Teriparatide US-Teriparatide N Mean (SD ) N Mean (SD ) N Mean (SD ) Baseline-adjusted E max (mg/dL) 101 0.314 (0.142) 101 0.333 (0.179) 102 0.341 (0.153) AUEC 0-t (mg.h/dL) 101 1.764 (1.305) 98 2.051 (1.816) 101 2.253 (1.732) T max (h) 101 5.457 (4.185) 101 5.023 (2.728) 102 5.252 (3.543) Baseline non-adjusted E max (mg/dL) 104 9.724 (0.268) 104 9.719 (0.272) 104 9.729 (0.261) AUEC 0-t (mg.h/dL) 104 222.215 (13.588) 104 223.389 (9.397) 104 223.972 (9.156) T max (h) 104 5.406 (4.149) 104 5.022 (2.691) 104 5.266 (3.510) Figure 1. Mean Serum Concentration vs. Time Curve for Teriparatide 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