A randomised Phase 3 study comparing the efficacy and safety of proposed denosumab biosimilar RGB-14-P and reference denosumab in women with postmenopausal osteoporosis.

• In women with postmenopausal osteoporosis, proposed denosumab biosimilar RGB-14-P demonstrated equivalent efficacy and pharmacodynamics, and similar immunogenicity and safety to reference denosumab. • RGB-14-P comprehensively replicates the therapeutic benefit of denosumab in a clinical setting. • Denosumab biosimilars, such as RGB-14, have potential to provide lower-cost alternatives to denosumab with comparable efficacy and safety. PURPOSE: To demonstrate the equivalence of the proposed denosumab biosimilar RGB-14-P and the reference denosumab (hereafter denosumab) in women with postmenopausal osteoporosis. METHODS: In this multicentre, double-blind, Phase 3 study (EudraCT 2020-006017-38; NCT05087030), participants were randomised 1:1 to subcutaneous RGB-14-P or denosumab 60 mg every 6 months, on Day 1 and Week 26, with follow-up to Week 52. Primary endpoints were percentage change from baseline (%CfB) in lumbar spine bone mineral density (BMD) at Week 52 and area under the effective curve (AUEC) of %CfB serum C-terminal telopeptide of type 1 collagen (CTX) to Week 26. Secondary endpoints included %CfB in total hip and femoral neck BMD, vertebral and non-vertebral fragility fractures, immunogenicity, and safety to Week 52. RESULTS: Overall, 473 participants were randomised and received study drug (RGB-14-P, n = 242; denosumab, n = 231). Both primary endpoints demonstrated equivalence of RGB-14-P and denosumab. Adjusted mean (95% CI) %CfB in lumbar spine BMD at Week 52 was 4.89 (3.55, 6.24) for RGB-14-P and 4.55 (3.22, 5.87) for denosumab (estimated difference, 0.34; 95% CI, - 0.40, 1.09). Geometric mean ratio in AUEC of %CfB in CTX concentration was 1.01 (95% CI, 0.98, 1.05; P = 0.494). There were no statistical differences in %CfB in total hip and femoral neck BMD. Incidence of vertebral or non-vertebral fragility fractures was comparable between treatments. Anti-drug antibody incidence was < 1% in both arms. Safety was comparable between groups. CONCLUSION: In women with postmenopausal osteoporosis, RGB-14-P demonstrated equivalent efficacy and pharmacodynamics, and similar immunogenicity and safety to denosumab.