Innovent Biologics presented promising one-year results from its Phase 2 clinical trial of efdamrofusp alfa (IBI302) in Chinese patients with neovascular age-related macular degeneration (nAMD) at the 2025 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Salt Lake City, Utah.
The randomized, double-masked, active-controlled study evaluated the efficacy, safety, and dosing intervals of high-dose IBI302—a novel recombinant human vascular endothelial growth factor receptor (VEGFR)-antibody human complement receptor 1 (CR1) fusion protein—compared to standard aflibercept treatment over a one-year period.
Extended Dosing Interval Shows Promise
The trial enrolled 132 subjects randomized equally across three treatment arms: IBI302 6.4 mg, IBI302 8.0 mg, and aflibercept 2.0 mg. Following initial loading doses, patients in the IBI302 groups received treatment at personalized intervals of either 8 or 12 weeks based on disease activity assessment at week 20, while the aflibercept group maintained a fixed 8-week dosing schedule.
Notably, over 80% of participants in both IBI302 groups maintained visual benefits with a 12-week dosing interval throughout the trial period, suggesting potential for reduced treatment burden compared to current standard therapies.
Competitive Efficacy Profile
The trial met its primary endpoint, with both IBI302 doses demonstrating non-inferior best-corrected visual acuity (BCVA) gains compared to aflibercept at week 40. Mean BCVA improvements from baseline were +10.5, +11.0, and +9.8 ETDRS letters for the IBI302 6.4 mg, IBI302 8.0 mg, and aflibercept 2.0 mg groups, respectively.
These visual improvements were sustained through week 52, with the IBI302 8.0 mg group showing the highest letter gain of +11.3 compared to baseline.
Superior Anatomical Improvements
IBI302 demonstrated superior anatomical efficacy compared to aflibercept. At week 52, central subfield thickness (CST) reductions from baseline were 154.58 μm for the IBI302 6.4 mg group and 174.69 μm for the IBI302 8.0 mg group, compared to 131.18 μm for the aflibercept group.
Perhaps most intriguing was the potential protective effect against macular atrophy (MA). Pooled analyses from two Phase 2 trials suggested that IBI302 treatment may reduce MA incidence at week 52 by nearly 40% compared to aflibercept (4.9% vs. 8.3%).
Novel Dual-Targeting Mechanism
IBI302 represents a first-in-class bispecific molecule that simultaneously targets the VEGF pathway and complement activation. This dual mechanism aims to address both the vascular and inflammatory components of nAMD pathogenesis.
"While anti-VEGF drugs remain the first-line therapy for nAMD, the frequency of intravitreal injections and follow-up visits can significantly impact patient compliance," said Professor Xiaodong Sun, Principal Investigator of the study and Head of National Center for Clinical Ophthalmology at Shanghai General Hospital. "Current drug development focuses on multi-target strategies and extended dosing intervals to reduce the treatment burden by decreasing injection frequency."
Safety Profile Comparable to Standard Treatment
The incidence of adverse events in both IBI302 groups was similar to the aflibercept group, with no cases of retinal vasculitis reported and no new safety signals identified throughout the trial.
Dr. Lei Qian, Senior Vice President of Clinical Development at Innovent, emphasized the significance of these findings: "High dose IBI302 demonstrates positive efficacy in visual acuity and anatomical improvements, while extending dosing intervals and showing potential anti-macular atrophy effects. These encouraging results establish a robust foundation for subsequent development."
Addressing Unmet Needs in nAMD Treatment
Age-related macular degeneration is a leading cause of vision loss among older adults, with the neovascular form characterized by abnormal blood vessel growth that can lead to rapid and severe vision deterioration if left untreated.
Current standard treatments require frequent intravitreal injections, typically every 4-8 weeks, creating a significant burden for patients and caregivers. The potential for a 12-week dosing interval with IBI302 could substantially reduce this treatment burden while maintaining efficacy.
Path Forward
Based on these positive Phase 2 results, Innovent plans to expedite the Phase 3 clinical trial program for IBI302. The company will continue collaborating with clinical experts to accelerate the development of this innovative therapy for patients with nAMD.
If successful in Phase 3 trials, efdamrofusp alfa could provide a valuable new treatment option that combines efficacy comparable to current standards with extended dosing intervals and potential protection against macular atrophy progression.
