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A Novel Bispecific Fusion Protein Targeting C3b/C4b and VEGF in Patients With nAMD: A Randomized, Open-Label, Phase
Huixun Jia1, Tong Li2, Junran Sun2
1From the Department of Ophthalmology (H.J., T.L., J.S., Y.G., H.L., H.W., J.C., W.L., F.W., X.S.) Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Ophthalmic Diseases (H.J., T.L., J.S., J.C., W.L., F.W. X.S.), Shanghai, China; Shanghai Key Laboratory of Fundus Diseases (H.J., F.W., X.S.) Shanghai, China.
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.
