Innovent’s efdamrofusp alfa meets Phase III endpoint in nAMD

Innovent Biologics (HKEX: 01801), the Suzhou- and San Francisco-based biopharmaceutical company, reported that its dual-target fusion protein efdamrofusp alfa (IBI302) met the primary endpoint of the Phase III STAR study in neovascular age-related macular degeneration, demonstrating non-inferiority to aflibercept in visual acuity gains at 52 weeks while enabling approximately 73% of participants to reach a 16-week dosing interval. The data position efdamrofusp alfa as the first domestically-developed extended-interval treatment for nAMD in China.

STAR is a Phase III, randomized, active-controlled study that enrolled 600 Chinese patients with nAMD, including 65% who were treatment-naïve. Participants received either efdamrofusp alfa 8 mg or aflibercept 2 mg, each beginning with three monthly loading doses. The aflibercept arm continued on fixed eight-week dosing, while the efdamrofusp alfa arm was assigned to 16-, 12-, or 8-week intervals based on disease activity assessments. The study runs for 100 weeks total.

At Week 52, the least squares mean change from baseline in best corrected visual acuity was 10.37 ETDRS letters for efdamrofusp alfa versus 10.11 letters for aflibercept, meeting the pre-specified non-inferiority margin. Approximately 86% of patients in the efdamrofusp alfa arm achieved dosing intervals of 12 weeks or longer, and 72.8% reached 16-week intervals. Among those on extended schedules, roughly 95% maintained their interval without retreatment through Week 52. The company also reported that 56.3% of participants showed no disease activity at Week 24, suggesting potential for further extension to 20-week dosing. Macular atrophy incidence at Week 52 was 1.5% in the efdamrofusp alfa group versus 2.9% with aflibercept, though this was not a pre-specified primary or key secondary endpoint.

The overall adverse event profile for efdamrofusp alfa was comparable to aflibercept, with most ocular events described as mild to moderate and resolving with observation or routine management. The company did not disclose rates of intraocular inflammation or endophthalmitis.

Efdamrofusp alfa is a recombinant bispecific fusion protein that combines a VEGF-binding domain at its N-terminus — targeting VEGF-A, VEGF-B, and placental growth factor — with a complement receptor 1 domain at its C-terminus that binds C3b and C4b to inhibit both classical and alternative complement pathways. The rationale for dual inhibition rests on evidence that complement activation contributes to chronic inflammation and photoreceptor damage in AMD independently of VEGF-driven neovascularization, and that suppressing both pathways may slow progression to macular atrophy.

The closest comparator in terms of extended dosing is faricimab (Vabysmo), the Roche/Genentech bispecific antibody targeting VEGF-A and angiopoietin-2, which gained approval in the US in 2022 for nAMD and diabetic macular edema. In the TENAYA and LUCERNE Phase III trials, faricimab enabled approximately 45% to 46% of nAMD patients to reach 16-week dosing intervals at one year. Innovent’s cross-trial comparison table reported the efdamrofusp alfa 16-week rate at 72.8% versus faricimab’s 44.9% to 45.7%, though cross-trial comparisons are limited by differences in study design, patient populations, and disease activity assessment criteria. Aflibercept 8 mg (Eylea HD), approved by the US FDA in 2023 for nAMD with 12- to 16-week dosing, represents an additional benchmark, but the STAR trial used aflibercept 2 mg on an 8-week schedule as its comparator.

Innovent stated it will prepare a New Drug Application submission in China based on these results. Complete data from the 100-week study period are expected to be presented at future academic conferences or in peer-reviewed publications. The company indicated it is also advancing lifecycle development for efdamrofusp alfa in other retinal indications, though it did not specify timelines for additional trials.