Post Hoc Analysis of a Phase 3 Trial on SB15 (Proposed Aflibercept Biosimilar): Assessment on Pre-to-Post Switching Efficacy and Safety in Neovascular Age-related Macular Degeneration

초록

Purpose : SB15, a proposed aflibercept biosimilar, demonstrated clinical equivalence to reference aflibercept (AFL) in neovascular age-related macular degeneration and results of 56-week phase 3 pivotal trial were previously reported. We performed a post hoc analysis to assess whether the comparable clinical outcomes were maintained after switching from AFL to SB15. Methods : 449 participants were randomized 1:1 at Week 0 to receive 3 consecutive monthly intravitreal injections of 2 mg (0.05 mL) of SB15 or AFL, followed by injection every 8 weeks up to Week 48. To assess pre-to-post switching efficacy and safety, the participants were re-randomized at Week 32 to continue treatment (AFL/AFL or SB15/SB15) or switch from AFL to SB15 (AFL/SB15). The primary endpoint was the change in best-corrected visual acuity (BCVA) from baseline to Week 8. All clinical endpoints were assessed through Week 56. The efficacy and safety in post-switching were compared with those in pre-switching. Using the data measured at the time of re-randomization (Week 32) prior to injection as a new baseline, a post hoc analysis was performed on efficacy endpoints, including changes in BCVA and central subfield thickness, to assess biosimilarity between two agents after switching (AFL/AFL vs AFL/SB15). Results : Of the 449 participants (SB15, n=224; AFL, n=225), 438 were re-randomized to SB15-continued (SB15/SB15, n=219), AFL-continued (AFL/AFL, n=108), and SB15-switched (AFL/SB15, n=111) groups. 425 (97.0%) completed up to Week 56. The new baseline (Week 32; prior to re-randomization) characteristics appeared comparable between AFL/SB15 and AFL/AFL. The efficacy was maintained post-switching as the mean BCVA letter score for AFL/SB15 was 65.3 at Week 32 (pre-switching) and 65.8 at Week 56 (post-switching) and for AFL/AFL was 65.2 at Week 32 and 65.8 at Week 56. The least squares mean change in BCVA from Week 32 to Week 56 was 0.2 and 0.0 letters for AFL/SB15 and AFL/AFL, respectively (difference: 0.3 [95% CI: -1.2 to 1.8] letters]). The safety and immunogenicity appeared similar between the two groups after switching. Conclusions : Our findings from this post hoc analysis were consistent with results from pivotal trial that efficacy and safety appeared comparable between AFL to SB15 and biosimilarity between these agents were maintained after switching.