Sustained Efficacy, Safety and Immunogenicity Following Single Switch from Reference Product Denosumab to FKS518 Proposed Biosimilar in Postmenopausal Women with Osteoporosis (Results from the Pivotal LUMIADE 3 Study)

Objectives There is considerable interest in transitioning patients to biosimilars to provide highly effective therapies while controlling costs. FKS518 is a denosumab biosimilar approved for use in patients with osteoporosis, with proven therapeutic efficacy to the reference product. Efficacy, safety and immunogenicity results after single treatment transition in the phase 3 study (LUMIADE-3, NCT04934072) are reported here.

Methods Postmenopausal osteoporotic women aged 55-85 with lumbar spine bone mineral density (LS-BMD) T-score ≤ −2.5 and ≥ −4.0 were recruited for this randomized, double-blind, parallel-group trial. Patients were randomized 1:1 for 3 60mg administrations of reference denosumab or FKS518, stratified by age and prior bisphosphonate use. At week 52 (W52), those on reference denosumab were re-randomized 1:1 to continue or switch to FKS518. Those on FKS518 continued their treatment. Efficacy and safety endpoints W52 to W78 included LS-BMD, BMD at femoral neck and total hip, occurrence of adverse events (AE), serious AEs, local tolerability and immunogenicity. Repeated measures analysis of percent change from baseline (%CfB) was performed. Safety parameters were reported descriptively for the 3 post-switch groups.

Results Patients were randomized to FKS518 (n=276) or reference denosumab (277). Clinically relevant increases in LS-BMD, femoral neck BMD, and total hip BMD were seen at W52 in both treatment groups. %CfB in LS-BMD, femoral neck BMD and total hip BMD were also similar between those who continued on reference denosumab (125) and those who switched to FKS518 (124) (Figure 1), with repeated measures analysis consistently showing the 95% CI for the difference between groups were narrowed around zero. No clinically meaningful differences in safety, tolerability or immunogenicity were observed after switching from reference denosumab to FKS518 compared to patients who continued with either treatment. The most frequently reported TEAEs were Nasopharyngitis and Upper respiratory tract infection (W52 to W78). Only 5 patients experienced injection site reactions during the 78-week study, none were serious, and no differences between treatments were seen. The number of patients with anti-drug antibodies was low.

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Figure 1:

LS-BMD, BMD at femoral neck and total hip (g/cm2) by DXA over time in patients receiving FKS518, reference denosumab and patients who transitioned from reference denosumab to FKS518 at W52 (ITT Analysis set)

Conclusion This study demonstrated therapeutic equivalence between FKS518 and reference denosumab and showed sustained efficacy after transitioning to FKS518, with no impact on safety or immunogenicity.