A randomized, double-blind, study to evaluate the efficacy, pharmacodynamics, safety and immunogenicity of FKS518 proposed biosimilar to denosumab with the originator in postmenopausal women with osteoporosis (LUMIADE-3 study).
Authors: Sadek Jouliana , Valter Ivo , de Souza Adriano , Szeles Peter , Monnet Joelle 
Published: July 2024

3155 Background: Biosimilars can increase patient access to treatment. FKS518 is a candidate biosimilar of denosumab, a RANKL inhibitor used in patients with bone metastases from certain solid tumors and in multiple myeloma. To establish biosimilarity, comparative studies are conducted in the most sensitive patient population to detect if there are clinically meaningful differences. LUMIADE-3 was designed to assess the safety and efficacy of FKS518 compared to the originator in postmenopausal women with osteoporosis (PMO). Methods: A randomized, double-blind, multicenter, 2-arm study recruited female patients aged 55 to 85 years with confirmed postmenopausal status and lumbar spine bone mineral density (LS-BMD) T-score ≤ -2.5 and ≥ -4.0, as measured by central dual-energy X-ray absorptiometry (DXA) assessment. Subjects with prior osteoporosis treatment that could add risk for cumulative effect or affect the interpretation of results were excluded. Patients were randomized and received three 60 mg administrations. At week 52, patients receiving denosumab originator were re-randomized to continue their treatment or switch to FKS518 for the third dose. Those receiving FKS518 continued receiving FKS518. The primary efficacy endpoint was the percent change from baseline in LS-BMD DXA at week 52. An analysis of the covariance model was used to compare the two treatments and two separate one-sided tests at alpha=0.05 were performed to assess equivalence. Secondary efficacy endpoints included the percent change from baseline in BMD at the femoral neck and total hip. Results: A total of 553 patients were randomized 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 groups. The results demonstrated therapeutic equivalence: the lower bound of the 90% CI for non-inferiority (-0.05) was above -1.45, and the upper bound of the 90% CI for non-superiority (1.20) was below 1.45. All secondary objectives were met. At week 52, a similar percent change from baseline in BMD at the femoral neck and total hip was observed between the two groups. 374 patients (67.6%) experienced treatment-emergent adverse events: 185 (66.8%) in the FKS518 group and 189 (68.5%) in the originator product group. Safety evaluation did not point to notable differences between FKS518 and the originator product groups. Conclusions: We demonstrated the therapeutic equivalence of FKS518 and originator product. The safety data showed similar safety profiles for the FKS518 and the originator product groups. Results from this study add to the totality of evidence supporting the similarity of FKS518 as a proposed biosimilar to denosumab originator product, a RANKL inhibitor used in patients with bone metastases from solid tumors. Clinical trial information: NCT04934072 .