Phase 3 study comparing the efficacy and safety of proposed biosimilar RGB-14-P with denosumab in postmenopausal women with osteoporosis: results from the transition (switch) phase.

UNLABELLED: Osteoporosis is a chronic condition requiring long-term management of fracture risk. Biosimilars provide the possibility of continuous use of well-established compounds. Proposed denosumab biosimilar RGB-14-P demonstrated equivalent efficacy and similar pharmacodynamics, immunogenicity, and safety to the reference denosumab. Transitioning from reference denosumab to RGB-14-P was associated with continued effectiveness and safety.

PURPOSE: To establish the therapeutic equivalence of RGB-14-P and reference denosumab (RD) in postmenopausal women with osteoporosis through demonstrating equivalent efficacy and similar safety, pharmacodynamics (PD), and immunogenicity when transitioning from RD to RGB-14-P.

METHODS: Patients (n = 188) who had received two 60-mg doses of RGB-14-P or RD (day 1 and week 26) in a randomised, blinded, controlled phase 3 study were re-randomised 1:1:1 at week 52 to continue RGB-14-P (n = 63) or RD (n = 63) or transition from RD to RGB-14-P (n = 62) and followed to week 78.

RESULTS: Gains in lumbar spine, hip, and femoral neck bone mineral density (BMD) observed in the first 52 weeks of treatment were further improved up to week 78 in all three groups, including patients who transitioned from RD to RGB-14-P. Incidences of new fragility fractures were comparable. Changes from baseline in serum PD markers (serum C-telopeptide of type I collagen and procollagen type I N-terminal propeptide) were maintained. The transition did not induce a discernible immunological reaction, and there were no clinically meaningful between-group differences in safety.

CONCLUSION: Treatment responses to RGB-14-P or RD seen during the first 52 weeks of treatment further improved to week 78; transitioning from RD to RGB-14-P had no discernible impact on efficacy, PD, immunogenicity, or safety. The totality of the evidence on the proposed biosimilar RGB-14-P available to date demonstrated structural and functional similarity as well as PK, PD, and therapeutic equivalence to reference denosumab, which suggests that RGB-14-P can be considered for long-term treatment, as well as a continuation of denosumab treatment.