All ocular treatment-emergent adverse events were intravitreal injection related and mild or moderate in severity.
New findings suggest intravitreal efdamrofusp alfa was well tolerated in patients with neovascular age-related macular degeneration (nAMD) in a phase 1b study.
Both low (2 mg) and high-dose (4 mg) regimens of efdamrofusp alfa were well-tolerated and all enrolled patients completed the treatment and all scheduled visits, with similar safety as other intravitreal anti-VEGF agents and complement inhibitors.
“More attention should be given to the potential risk of exudative choroidal neovascularization (CNV) in the subsequent trials of efdamrofusp alfa, although the safety profile of complement inhibition in eyes appeared to be favorable at the current stage,” wrote study author Xiaodong Sun, MD, PhD, Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine.
The advent of anti-vascular endothelial growth factor (anti-VEGF) agents has proven an important innovation in the treatment of nAMD, but challenges persist with maintenance of the initial vision gains. Long-term use of anti-VEGF therapies for nAMD may activate the complement system, which can further stimulate the formation of CNV or geography atrophy (GA).
The current randomized, open-label, aflibercept-controlled, multiple ascending dose phase 1b study looked to evaluate the tolerability and safety of efdamrofusp alfa in patients with nAMD. Efdamrofusp alfa is a novel bispecific decoy receptor fusion protein that acts independent through neutralizing both C3b/C4b and VEGF.
A total of eighteen eligible patients aged 50 years or older with active choroidal neovascularization (CNV) secondary to nAMD were screened from two hospitals in two provinces in China. One eye per patient was designated as the study eye.
The first nine patients were randomized 2:1 to receive efdamrofusp alfa 2 mg (n = 6) at week 0, 4, and 8, or aflibercept 2 mg at week 0, 4, 8, and 16 (n = 3). Following the dose limiting toxicity assessment, an additional nine patients were randomized 2:1 to intravitreally receive efdamrofusp alfa 4 mg at week 0, 4, 8, or aflibercept 2 mg at weeks 0, 4, 8, and 16. The follow-up was performed until week 20.
Between May 2020 and February 2021, all 18 patients completed the treatment and the study and no patients received rescue therapy. The mean BCVA score was higher in the efdamrofusp alfa 4 mg group at baseline, while the aflibercept group had greater central subfield thickness (CST) and lower CNV area at baseline.
Both regiments of efdamrofusp alfa were well-tolerated in the study, with efdamrofusp alfa demonstrating an overall favorable safety profile in patients with nAMD. Neither dose-limiting toxicity events or ocular serious adverse events were reported.
Ocular treatment-emergent adverse events were reported in two patients receiving efdamrofusp alfa 2 mg and four patients each in efdamrofusp alfa 4 mg and aflibercept group. All were mild or moderate in severity and related to the intravitreal injection procedure.
The findings indicated both efdamrofusp alfa and aflibercept treatment led to BCVA gain. Individuals receiving efdamrofusp alfa 4 mg had rapid and robust improvement in visual acuity as early as one week after the first dose, peaked at week 4 and maintained throughout the study.
At Week 20, the mean changes from baseline in BCVA were 5.64, 8.93, and 7.92 letters for patients receiving efdamrofusp alfa 2 mg, efdamrofusp alfa 4 mg, and aflibercept 2 mg, respectively.
Moreover, efdamrofusp alfa and aflibercept treatment led to profound decrease in CST, which was evident one week after the first dose and plateaued at week 8 in all dose groups. A reduction in CNV was observed at week 12 and week 20 in all groups.
The study, “A novel bispecific fusion protein targeting C3b/C4b and VEGF in Patients with nAMD: A Randomized, Open-label Phase 1b Study,” was published in the American Journal of Ophthalmology.