Randomized Trial of Biosimilar XSB-001 versus Reference Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration
Abstrakt
Objective: To evaluate the efficacy, safety, and immunogenicity of a ranibizumab biosimilar candidate (XSB001) versus reference product (Lucentis) for neovascular age-related macular degeneration (nAMD).Design: Phase III, multicenter, randomized, double-masked, parallel-group study.Participants: Patients with nAMD.Methods: Eligible patients were randomized (1:1) to receive intravitreal injections of XSB-001 or reference ranibizumab (0.5 mg [0.05 ml]) in the study eye once every 4 weeks for 52 weeks. Efficacy and safety assessments continued through 52 weeks of treatment.
Main Outcome Measures: Primary end point was change from baseline in best-corrected visual acuity (BCVA) by ETDRS letters at week 8. Biosimilarity was concluded if the 2-sided 90% confidence interval (CI) (United States) or 95% CI (rest of world) for the difference in least-squares (LS) mean change in BCVA at week 8 between treatment groups was within the predefined equivalence margin of +/- 3.5 letters.Results: In total, 582 patients (n = 292 XSB-001, n = 290 reference ranibizumab) were randomized.
Mean age was 74.1 years, most patients (85.2%) were White, and 55.8% were women. Mean BCVA score at baseline was 61.7 and 61.5 ETDRS letters in the XSB-001 and reference ranibizumab groups, respectively.
At week 8, the LS mean (standard error [SE]) change in BCVA from baseline was 4.6 (0.5) ETDRS letters in the XSB-001 group and 6.4 (0.5) letters in the reference ranibizumab group (LS mean [SE] treatment difference:-1.8 [0.7] ETDRS letters; 90% CI,-2.9 to-0.7; 95% CI,-3.1 to-0.5). The 90% CI and 95% CI for LS mean difference in change from baseline were within the predefined equivalence margin.
At week 52, LS mean (SE) change in BCVA was 6.4 (0.8) and 7.8 (0.8) letters, respectively (LS mean [SE] treatment difference,-1.5 [1.1] ETDRS letters; 90% CI,-3.3 to 0.4; 95% CI,-3.6 to 0.7). There were no clinically meaningful differences between treatments in anatomical, safety, or immunogenicity end points through week 52.Conclusions: XSB-001 demonstrated biosimilarity to reference ranibizumab in patients with nAMD.
Treatment with XSB-001 for 52 weeks was generally safe and well tolerated, with a safety profile similar to the reference product.