Lusacomfar Alfa (GEM103): A Comprehensive Report on a Recombinant Complement Factor H

1. Executive Summary

Lusacomfar Alfa, also widely known by its research code GEM103, is a recombinant human complement factor H (CFH).[1] It was developed primarily as a potential therapeutic intervention for dry age-related macular degeneration (AMD), with a particular focus on patients with geographic atrophy (GA) harboring specific CFH genetic risk variants.[3] In addition to its ophthalmological development, Lusacomfar Alfa received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of atypical hemolytic uremic syndrome (aHUS).[5]

Initial Phase 1 and early Phase 2a clinical investigations of Lusacomfar Alfa administered via intravitreal injection for AMD demonstrated a favorable safety and tolerability profile, along with evidence of local biological activity, including sustained supraphysiological levels of CFH in the aqueous humor and modulation of complement biomarkers.[7] These early findings supported its progression into further clinical studies.

However, subsequent Phase 2a trials evaluating Lusacomfar Alfa in patients with GA secondary to dry AMD (ReGAtta study) and as an adjunctive therapy in wet AMD were discontinued by the original developer, Gemini Therapeutics.[9] While the company initially stated that these discontinuations were because the studies had met their primary objectives of assessing safety and tolerability, other reports and the overall context suggest that a lack of demonstrated clinical efficacy in slowing disease progression in AMD was a pivotal factor.[10]