Aflibercept Biosimilar SB15 Demonstrates Comparable Efficacy, Safety

The aflibercept biosimilar SB15 showed comparable safety, efficacy, pharmacokinetics, and immunogenicity when compared with the reference product in patients with neovascular age-related macular degeneration (nAMD) who switched to the biosimilar and those who did not, according to a study published in BMJ Open Ophthalmology.¹

“Although evidence suggests that switching from reference product to its biosimilar is as effective and safe as continuing treatment with the reference product, the currently available data on switching to ophthalmic anti-vascular endothelial growth factor (VEGF) biosimilars is not sufficient yet to draw definitive conclusions,” wrote Se Joon Woo, MD, PhD, professor of ophthalmology at Seoul National University Bundang Hospital, and colleagues.

SB15 is currently being studied as a potential treatment for nAMD. Previous research has proved similarity between both drugs regarding the structural, physicochemical, and biological components, and the results of a phase 3 study demonstrated clinical equivalence up to week 32.²

In the prospective, double-masked, randomized, multicenter phase 3 trial, subjects were randomized 1:1 to receive either intravitreal injection of 2 mg (.05 mL) SB15 (n = 224) or aflibercept (n = 225). At week 32, patients were rerandomized to continue to receive SB15 (n = 219) or aflibercept (n = 108) or be switched from aflibercept to SB15 (AFL/SB15; n = 111) to week 56.

Secondary efficacy endpoints included changes from baseline to week 56 in central subfield thickness (CST), total retinal thickness (TRT), and best-corrected visual acuity (BCVA). Other endpoints were safety, pharmacokinetics, and immunogenicity. At baseline, demographics and disease characteristics were similar between the SB15 and aflibercept cohorts.

At week 56, the least squares mean (LSmean) change in BCVA from baseline was 7.4 letters in the SB15 group and 7.0 letters in the aflibercept group (difference [95% confidence interval (CI)] = .4 [−2.5 — 3.2]). Changes observed from baseline to week 56 in the anatomical endpoint CST were −119.2 µm in those receiving SB15 and −126.6 µm in the aflibercept cohort (difference [95% CI] = 7.4 µm [−6.11 — 20.96]). LSmean changes in TRT in the SB15 group and aflibercept group were −132.4 µm and −136.3 µm, respectively (difference [95% CI] = 3.9 µm [−18.35 to 26.10]). Pharmacokinetics, immunogenicity, and safety were also similar across treatment arms.

Regarding the switching and non-switching cohorts, similar LSmean changes in BCVA from baseline to the 56-week mark were observed, with those in the non-switch group having a change of 7.8 letters compared with the switch group, which reported a change of 7.9 letters (difference [95% CI] = 0.0 [−2.8 — 2.8]).

The incidence and characteristics of treatment-emergent adverse events (TEAEs) were similar between patients in the SB15 cohort (36.5%, n = 80/219), aflibercept cohort (29.8%, n = 31/104), and the AFL/SB15 cohort (35.1%, n = 39/111). Most TEAEs were categorized as mild or moderate and unrelated to the study drug, with the most common ocular events reported as reduced visual acuity and cataract.

Investigators added, to their knowledge, this was the first study to provide clinical data on switching from reference aflibercept to a proposed biosimilar. However, the small sample size of the aflibercept and AFL/SB15 groups compared with the SB15 group was considered a limitation. Therefore, they encourage the results of the secondary endpoint analysis to be interpreted with caution.

“Overall, these findings support the safe and effective use of SB15 for the treatment of retinal diseases not only in aflibercept-naïve participants, but also in participants previously treated with reference aflibercept,” investigators concluded.

References

1. ^{Woo SJ, Sadda SR, Bradvica M, et al. Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial. BMJ Open Ophthalmol. 2023;8(1):e001561. Published 2023 Dec 19. doi:10.1136/bmjophth-2023-001561}
2. ^{Woo SJ, Bradvica M, Vajas A, et al. Efficacy and safety of the Aflibercept Biosimilar Sb15 in Neovascular age-related macular degeneration: a phase 3 randomized clinical trial. JAMA Ophthalmol 2023;141:668–76. doi:10.1001/jamaophthalmol.2023.2260}