A Prospective, Active-controlled, Randomized, Double-blind, Multicenter, Phase III Study to Compare the Safety and Efficacy of Biosimilar Denosumab vs Reference Denosumab in the Treatment of Postmenopausal Osteoporosis.

Denosumab, a human monoclonal antibody that exhibits strong affinity and specificity for the receptor activator of nuclear factor-kappa B ligand (RANK-L), is essential in regulating bone turnover. Its inhibition of RANK-L decreases bone resorption by preventing the development, function, and survival of osteoclasts. The objective of the study was to evaluate and compare the efficacy and safety of biosimilar denosumab with the reference product, Prolia (denosumab), in Indian women suffering from postmenopausal osteoporosis. This phase III study was a prospective, active-controlled, randomized, double-blind trial that included postmenopausal women diagnosed with osteoporosis. Participants were randomly allocated in a 2:1 ratio to receive either the biosimilar denosumab (Treatment A) or the reference denosumab (Prolia®; Treatment B). All participants also received daily supplementation of 500 international units (IU) of vitamin D3 and 1000 mg calcium. The primary outcomes measured were the bone mineral density (BMD) percentage change at the lumbar spine and the neck of femur, while the secondary endpoint assessed changes in biomarkers from baseline at months 6 and 12. The lumbar spine BMD percentage change for group A vs group B from baseline to month 6 was 5.69 ± 0.88 (p < 0.0001) vs 5.08 ± 1.19 (p < 0.0001), and at 12 months was 7.26 ± 1.05 (p < 0.0001) vs 7.31 ± 1.40 (p < 0.0001), demonstrating equivalent efficacy. Both treatment groups showed statistically significant improvement in femoral neck BMD at 12 months. No statistically significant difference was noted in the ln-transformed primary pharmacokinetic parameters, including C-max, AUC0-120d, and AUC0-∞. Biosimilar denosumab was comparable to reference denosumab with respect to its efficacy, safety, pharmacokinetics (PK), pharmacodynamics, and immunogenicity in women with postmenopausal osteoporosis. Thus, biosimilar denosumab is expected to improve the quality of life in osteoporotic patients at affordable prices.