Aflibercept Biosimilar Demonstrates Equivalent Efficacy for Neovascular Age-Related Macular Degeneration

SB15, a biosimilar to aflibercept— a vascular endothelial growth factor (VEGF) inhibitor that treats neovascular age-related macular degeneration (nAMD)—demonstrated equivalent efficacy to the reference product, according to the results of a recent phase 3 study published in JAMA Network Open.

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“Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy,” the study authors wrote in their analysis.

nAMD— the primary cause of blindness and severe vision loss in older persons—is associated with increased expression of VEGF. The standard of care for nAMD and other VEGF-mediated diseases is VEGF inhibition therapy, including aflibercept.

SB15 has already been successfully evaluated for structure, physiochemical, and biological similarity, but investigators need to know whether SB15 has an equivalent efficacy and a comparable safety, pharmacokinetics, and immunogenicity to aflibercept. From June 2020 to March 2022, investigators conducted a 1:1 randomized phase 3, double-masked, parallel group, multicenter study (NCT04450329) to determine these endpoints.

The study enrolled eligible patients aged 50 years and older with nAMD who received a 2 mg intravitreal injection of SB15 or ALF at weeks 0, 4, and 8, then every 8 weeks. Patients were randomized again at week 32 to either continue initial treatment or switch to the other injection.

The study’s primary endpoint was squares mean (SE) change in best-corrected visual acuity (BCVA)—a type of ophthalmic examination that uses letters to detect symptoms of macular degeneration—from baseline to week 8 (within predefined margins of 3 letters). Secondary endpoints were change in BCVA from baseline to week 32, safety, pharmacokinetics, and immunogenicity.

At week 8, SB15 met the primary endpoint with change of 6.7 letters compared to aflibercept at 6.6 letters. At week 32, SB15 created change from baseline in BCVA with SB15 was 7.6 letters compared to 6.5 letters with aflibercept. SB15 also demonstrated comparable safety, pharmacokinetics, and immunogenicity to aflibercept for nAMD.

The pharmacokinetics of both treatments were similar. Both had comparable pre- and post-dose serum concentrations, which suggests that multiple doses do not result in accumulation in the plasma, according to the study. In addition, neither SB15 nor aflibercept led to high occurrence of antidrug antibody positivity. However, among those who were antidrug antibody positive, there was not a high occurrence of intraocular inflammation.

Further, investigators did not observe any new safety signals or clinically relevant differences in treatment-emergent adverse events (TEAEs). TEAEs occurred in 47.8% of patients treated with SB15 and 43.8% of patients treated with aflibercept.

The study contains some limitations, the first of which being that the study population was mainly Asian and White, leading to inadequate racial diversity. In addition, only 32 weeks of data are currently available. While investigators are collecting longer-term evidence (56 weeks) about the efficacy and safety of switching doses, those results have not yet been made available.

“The similarity of our findings to these previous results further substantiates the herein reported data and supports generalization of the demonstrated equivalent efficacy between SB15 and [aflibercept],” the study authors wrote in the article.

Reference

Woo S, Bradvica M, Vajas A. Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. Published online June 8, 2023. doi:10.1001/jamaophthalmol.2023.2260