P078 A randomised, controlled, double-blind study to evaluate the bioequivalence of FKS518 proposed biosimilar to denosumab with the originator in postmenopausal women with osteoporosis (LUMIADE-3 Study)

Background/Aims Denosumab treatment is growing with the ageing of rheumatic patients, and biosimilars can increase patients’ access to treatment. FKS518 is a candidate biosimilar to denosumab, a RANKL inhibitor used in patients with osteoporosis. To establish biosimilarity with the original biologic, the LUMIADE-3 study (NCT04934072) was designed to assess the safety and efficacy of FKS518 compared to the originator. Methods A randomised controlled, double-blind, multi-centre study on postmenopausal females aged 55-85 years with lumbar spine bone mineral density (LS-BMD) T-score between -2.5 and -4.0 measured by DXA scan. Patients were randomised at a 1:1 ratio for three 60 mg administrations. At week 52, patients receiving denosumab originator product were re-randomised to continue their treatment or switch to FKS518 for the third dose. Those receiving FKS518 continued receiving FKS518. The primary endpoints included the percent change from baseline in LS-BMD DXA at week 52 and the area under the effect curve (AUEC) of serum C-terminal cross-linking telopeptide of type 1 collagen (CTX) up to Week 26. Secondary efficacy endpoints included the percent change from baseline in BMD at femoral neck and total hip. An analysis of the covariance model was used to compare the two treatments. The difference in mean percent change from baseline to Week 52 in LS-BMD and the ratio of means of AUEC (0-W26) CTX along with corresponding 95% Confidence Intervals (CI) were calculated to assess equivalence. FKS518 was considered equivalent to the originator if the 95% CI for LS-BMD lay entirely within the equivalence interval of [-1.45%, 1.45%], and the 95% CI for AUEC (0-W26) lay within the equivalence interval of (0.89, 1.12) ng*h/L. Results 553 patients were randomised to FKS518 (n = 276) or the originator (n = 277). Clinically relevant increases in LS-BMD were evident at week 52 in both the FKS518 and originator product group; least square mean and standard error percent LS-BMD change from baseline were 5.74 (0.315) and 5.07 (0.321) for FKS518 and originator respectively. The 95% CI difference in mean percent change at Week 52 in LS-BMD was equal to [0.04%, 1.29%]. The 95% CI for the ratio of geometric least squares means for AUEC (0-W26) CTX was (0.99,1.04) ng*h/L. Therapeutic equivalence was demonstrated based on both efficacy and pharmacodynamics. All secondary study objectives were met. The safety evaluation did not indicate notable differences between the two treatments; 374 (67.6%) patients experienced treatment emergent adverse events during the 52-week core period: 185 (66.8%) in the FKS518 group and 189 (68.5%) in the originator product group. Conclusion The study demonstrated therapeutic equivalence of FKS518 with the originator and showed similar safety profiles. This study results followed positive preclinical and pharmacokinetic results corroborating the similarity of FKS518 as a proposed biosimilar to denosumab originator product, a RANKL inhibitor. Disclosure I. Valter: None. P. Szeles: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. A. De Souza: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study. J. Sadek: Other; Employee of Fresenius Kabi US - Sponsor of the study. J. Sykes: Other; Employee of Fresenius Kabi UK - Sponsor of the study. J. Morais: Other; Employee of Fresenius Kabi UK - Sponsor of the study. J. Monnet: Other; Employee of Fresenius Kabi SwissBioSim - Sponsor of the study.