Efdamrofusp alfa: an insight into the novel drug and its use in age-related macular degeneration.

Abstract

Purpose: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in older adults, with its prevalence rising globally. This review aims to explore the potential of Efdamrofusp alfa (EA), a novel bispecific decoy receptor fusion protein targeting both VEGF and complement pathways, in treating neovascular AMD (nAMD).

Methods: A comprehensive literature search was conducted across PubMed, Cochrane and Embase till March 2025 to find articles evaluating the efficacy of EA in the treatment of neovascular AMD. Observations from early pre-clinical studies and clinical trials were analyzed to determine the efficacy and safety of EA.

Results: A total of five preclinical and clinical studies were included, encompassing 66 animal subjects and 880 human participants. Efdamrofusp alfa (IBI302) neutralizes both C3b/C4b and VEGF, demonstrating anti-angiogenic effects in preclinical models. Clinical trials examined intravitreal doses ranging from 0.05 mg to 4.00 mg. EA showed efficacy in reducing central retinal thickness and improving visual acuity, with a safety profile comparable to existing anti-VEGF treatments. Treatment-emergent adverse events (TEAEs) included conjunctival hemorrhage, ocular hypertension, and keratitis, which were similar to those observed with other intravitreal anti-VEGF drugs. The drug demonstrated noninferiority to aflibercept in improving best-corrected visual acuity (BCVA) and significantly reduced central subfield thickness.

Conclusions: Efdamrofusp alfa shows promise as a novel treatment for nAMD, potentially offering improved efficacy over current anti-VEGF therapies. Nonetheless, further large-scale randomized clinical trials are essential to confirm its efficacy and safety in broader populations. The dual-inhibition strategy provides a new avenue for personalized AMD treatment, particularly for patients unresponsive to monotherapies.