A Novel Bispecific Fusion Protein Targeting C3b/C4b and VEGF in Patients With nAMD: A Randomized, Open-Label, Phase 1b Study.

PURPOSE:To evaluate the safety, tolerability, and efficacy of efdamrofusp alfa in patients with neovascular age-related macular degeneration (nAMD). DESIGN:Prospective randomized, open-label, multiple ascending-dose, phase 1b study. METHODS:Patients aged 50 years or older with active choroid neovascularization (CNV) secondary to nAMD were screened from 2 hospitals in 2 provinces in China. The first 9 patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 2 mg at weeks 0, 4, and 8 or aflibercept 2 mg at weeks 0, 4, 8, and 16. After the dose-limiting toxicity assessment, 9 additional patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 4 mg at weeks 0, 4, and 8 or aflibercept 2 mg at weeks 0, 4, 8, and 16. All patients were followed until week 20. Primary outcomes were safety and tolerability of efdamrofusp alfa. Secondary outcomes included changes from baseline in best-corrected visual acuity (BCVA), central subfield thickness (CST) as measured by spectral domain optical coherence tomography (SD-OCT), and CNV area as measured by fluorescein angiography (FA). RESULTS:A total of 18 patients were enrolled. Six each of them received efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg, or aflibercept 2 mg, respectively. No dose-limiting toxicity was reported, and all patients completed the study. No ocular serious adverse events were reported. All ocular treatment-emergent adverse events were intravitreal injection related and were mild or moderate in severity. At week 20, mean changes from baseline in BCVA were 5.64 ± 3.56, 8.93 ± 3.59, and 7.92 ± 3.55 letters for patients receiving efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg and aflibercept 2 mg, respectively. Meanwhile, CST and CNV area reductions indicative of anatomic improvement were observed in the majority of the patients receiving both doses of efdamrofusp alfa and aflibercept. CONCLUSIONS:Intravitreal efdamrofusp alfa dosed up to 4 mg every 4 weeks was well tolerated in nAMD patients with similar vision acuity and anatomic improvements.