Comparative Clinical and Therapeutic Landscape of Aflibercept Biosimilars (YESAFILI), High-Dose Aflibercept 8 mg (EYLEA HD), and Faricimab (VABYSMO): A Structured Narrative Review

Abstract: Reference aflibercept 2 mg (EYLEA; Regeneron/Bayer) remains a foundational therapy for neovascular age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion, supported by high binding affinity for vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor, along with well-established durability and flexible dosing approaches. The retinal therapeutic landscape is evolving with the introduction of high-dose aflibercept 8 mg (EYLEA HD; Regeneron/Bayer), faricimab (VABYSMO; Roche), and biosimilar aflibercept such as YESAFILI (Biocon Biologics), each representing distinct pharmacologic and clinical strategies. This structured narrative review synthesizes clinical trial and real‑world evidence across these three approaches, with a focus on efficacy, durability, safety, and system-level considerations. A predefined literature search of MEDLINE, Embase, and major ophthalmology conference proceedings was used to identify relevant evidence published from 2015 to 2026. Direct head-to-head evidence among these approaches is limited; therefore, comparisons across separate clinical development programs are descriptive and should be interpreted cautiously. In their respective clinical development programs, high-dose aflibercept and faricimab supported extended dosing intervals with non-inferior visual outcomes relative to standard aflibercept comparators, while biosimilar aflibercept demonstrated clinical equivalence to reference aflibercept with potential economic advantages. Differences remain in long-term real‑world data maturity, safety signal characterization, and implementation considerations. These therapies represent complementary strategies—dose escalation, mechanistic innovation, and molecular equivalence—requiring individualized, evidence-based clinical decision-making in an increasingly complex treatment paradigm. Keywords: aflibercept biosimilar, reference aflibercept 2 mg, high-dose aflibercept 8 mg, faricimab, vascular endothelial growth factor, VEGF, retinal disease treatment