Efficacy and Safety of Efdamrofusp Alfa versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized, Double-Masked, Active-Controlled, Noninferiority, Phase II Trial.

Purpose: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD).

Design: Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study.

Participants: A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled.

Methods: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week 52.

Main Outcome Measures: The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval [CI]).

Results: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, and +12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups.

Conclusions: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.