SAT0451 COMPARISON OF PHARMACOKINETIC, PHARMACODYNAMIC AND SAFETY OF A TERIPARATIDE BIOSIMILAR AND REFERENCE TERIPARATIDE

Abstract

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-tand 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.Table 1.Summary of Statistical Analysis of Pharmacokinetic Parameters of TeriparatideParametersNGLSMNGLSMRatio (T/R1) %90% Confidence IntervalTeriparatide Biosimilar (T)EU-Teriparatide (R1)lnCmax(pg/mL)10499.31410499.229100.195.50 - 104.89lnAUC0-t(pg.h/mL)103130.402103129.067101.096.37 - 105.93lnAUC0-∞(pg.h/mL)103150.589103144.887103.999.19 - 108.90Teriparatide Biosimilar (T)US-Teriparatide (R2)Ratio (T/R2) %lnCmax(pg/mL)10499.25510496.397103.098.74 - 107.37lnAUC0-t(pg.h/mL)102131.212102126.837103.498.90 - 108.21lnAUC0-∞(pg.h/mL)102150.564102143.860104.799.88 - 109.67GLSM: Geometric least squares mean; N: Number of subjects.Table 2.Summary of Corrected Total Serum Calcium Levels after Administration of TeriparatideParameterTeriparatide BiosimilarEU-TeriparatideUS-TeriparatideNMean (SD)NMean (SD)NMean (SD)Baseline-adjustedEmax(mg/dL)1010.314 (0.142)1010.333 (0.179)1020.341 (0.153)AUEC0-t(mg.h/dL)1011.764 (1.305)982.051 (1.816)1012.253 (1.732)Tmax(h)1015.457 (4.185)1015.023 (2.728)1025.252 (3.543)Baseline non-adjustedEmax(mg/dL)1049.724 (0.268)1049.719 (0.272)1049.729 (0.261)AUEC0-t(mg.h/dL)104222.215 (13.588)104223.389 (9.397)104223.972 (9.156)Tmax(h)1045.406 (4.149)1045.022 (2.691)1045.266 (3.510)Figure 1.Mean Serum Concentration vs. Time Curve for TeriparatideConclusion: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 fileDisclosure 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