Objectives: To demonstrate therapeutic equivalence of the proposed denosumab biosimilar FKS518 to the originator denosumab (US-licensed Prolia®, reference product), a potent antiresorptive biologic that increases bone mineral density (BMD) and reduces the risk of fractures, in women with postmenopausal osteoporosis.

Methods: This 78-week double-blind, controlled, randomized, multicenter, multiple-dose, 2-arm, parallel-group study compared the efficacy (BMD), pharmacodynamic (bone biomarkers), safety, tolerability, and immunogenicity profiles of FKS518 with those of reference denosumab in women with postmenopausal osteoporosis. Primary-percentage change from baseline to 52 weeks in lumbar spine BMD and area under the effect curve from baseline to week 26 of serum C-terminal cross-linking telopeptide of type 1 collagen-and secondary results from the 52-week core treatment period are reported here.

Results: Postmenopausal women with osteoporosis were randomized to receive 60 mg of FKS518 (n = 277) or reference denosumab (n = 276) every 26 weeks. Demographics, baseline characteristics and medical history were similar between treatment groups. Therapeutic equivalence of FKS518 and reference denosumab was demonstrated for efficacy and pharmacodynamic characteristics. All sensitivity analyses, supportive estimands, secondary efficacy, and pharmacodynamic endpoint analyses consistently showed similarity between the 2 products. Safety outcomes were consistent with the known safety profile of denosumab and were comparable between FKS518 and reference denosumab. Immunogenicity was infrequently observed and similar between the FKS518 and the reference denosumab groups.

Conclusion: This study demonstrated therapeutic equivalence of, and comparable pharmacokinetics, safety, and immunogenicity profiles between FKS518 and reference denosumab, completing the clinical evidence to propose FKS518 as a biosimilar to denosumab.