Phase III Randomized Clinical Trial Comparing SB15 with Reference Aflibercept in Neovascular Age-Related Macular Degeneration

초록

Purpose : SB15 is a proposed biosimilar to the reference aflibercept (AFL). Equivalence of primary endpoint [change from baseline in best corrected visual acuity (BCVA) at Week 8] and comparable efficacy, safety, immunogenicity and pharmacokinetics (PK) up to 32 weeks between SB15 and AFL in patients with neovascular age-related macular degeneration (nAMD) were previously reported (Woo et al., AAO 2022). Here we present the results up to 56 weeks. Methods : In this randomized, double-masked, multicenter study, nAMD patients were randomized 1:1 to receive either 2 mg SB15 (n=224) or AFL (n=225) every 4 weeks (q4w) for 3 consecutive intravitreal injections, followed by treatment q8w through Week 48. At Week 32, patients were re-randomized to either continue on their treatment (SB15/SB15 or AFL/AFL) or switch from AFL to SB15 (AFL/SB15). Efficacy, safety, immunogenicity and PK were assessed up to Week 56. Results : Of the 449 patients, 438 patients were re-randomized at Week 32; continuing SB15 (SB15/SB15, n=219), continuing AFL (AFL/AFL, n=108), switching from AFL to SB15 (AFL/SB15, n=111); and total 425 patients completed 56-weeks of study. During the study, the improvements in BCVA up to Week 56 were comparable between treatment groups (Fig 1, 2). LS mean BCVA letter change from baseline to Week 56 was 7.3 for SB15 (n=224) vs 6.4 for AFL (n=113); 7.9 for AFL/SB15 vs 7.5 for AFL/AFL. Comparability in anatomical outcomes was demonstrated in all treatment groups up to Week 56. The safety, immunogenicity, and PK were also comparable between SB15/SB15 and AFL/AFL, as well as between AFL/SB15 and AFL/AFL up to Week 56 after re-randomization at Week 32. No new intraocular inflammation occurred or anti-drug antibodies developed after switching in the AFL/SB15 group. Conclusions : SB15 demonstrated similar efficacy, safety, immunogenicity and PK compared with AFL up to Week 56. Switching from AFL to SB15 had no treatment-emergent issues such as loss of efficacy, increased adverse events or increased immunogenicity.