A Phase 3 Multicenter, Double-Blind Study Comparing Efficacy, Safety, Immunogenicity, and Pharmacokinetics of Alkem's Biosimilar Teriparatide Versus Reference Teriparatide in Postmenopausal Osteoporosis.

Objective: The primary purpose of this study was to compare the efficacy and safety of proposed biosimilar teriparatide with reference teriparatide in patients of postmenopausal osteoporosis. The secondary objectives were to assess the pharmacodynamic response of study drugs in postmenopausal osteoporosis and to assess the pharmacokinetic profile of biosimilar and reference teriparatide in a subset of subjects (a total of 30 evaluable subjects i.e., 15 subjects in reference arm and 15 subjects in biosimilar arm).

Methods: A prospective, active-controlled, randomized, double-blind, phase III study included postmenopausal women (50-80 years of age) with at least 5 years since menopause diagnosed with osteoporosis ( ≤ -2.5 SD at lumbar spine or femoral neck) randomized 2:1 to receive either Alkem's biosimilar teriparatide or reference teriparatide 20 μg once daily subcutaneously for 48 weeks. All subjects received calcium 1000 mg and vitamin D3 500 IU once daily orally. The primary efficacy endpoint was percent change in bone mineral density (BMD) at lumbar spine and femoral neck from baseline to 48 weeks. Safety outcomes, pharmacokinetics, and immunogenicity were also evaluated. Secondary endpoints included change from baseline in pharmacodynamic parameters like serum P1NP, which were analyzed at randomization, at week 12, 24, and 48.

Results: In total, 177 patients (114 in biosimilar group and 63 in reference group) were randomized. The percent change from baseline to 48 weeks in lumbar spine BMD (least square mean [LSM] ± standard error [SE]) was 8.58% ± 0.85 in the biosimilar group and 8.02% ± 1.23 in the reference group. The estimated between-group difference (95% confidence interval [CI]) was -0.56% (-2.43% to 3.54%) within the prespecified noninferiority margin (- 2.43%), which indicates noninferiority of biosimilar teriparatide compared to reference teriparatide. The percent change in femoral neck BMD from baseline to 48 weeks (LSM ± SE) was 3.94% ± 0.83 in the biosimilar group and 2.50% ± 1.20 in the reference group. The estimated between-group difference (95% CI) was 1.44% (-1.44% to 4.32%) within the prespecified noninferiority margin (-1.44%) indicating noninferiority of biosimilar teriparatide compared to reference teriparatide. Changes in P1NP (serum procollagen type 1 N terminal pro-peptide) were also similar between the groups. Safety profiles, including immunogenicity, were comparable.

Conclusion: This study established noninferiority, along with comparable safety and immunogenicity between Alkem's biosimilar teriparatide and reference teriparatide in patients with postmenopausal osteoporosis.

Trial Registration: CTRI number: CTRI/2018/05/014254.