ARVO 2026: Durability and dual targeting push retinal therapy beyond the anti-VEGF baseline

Reducing the burden of frequent intravitreal injections while maintaining disease control remains a central challenge in the management of retinal vascular disease. Three presentations at the Association for Research in Vision and Ophthalmology (ARVO) 2026 annual meeting, May 3 to 7 in Denver, Colorado, highlighted new data on extending treatment durability and broadening therapeutic targets in retinal vascular disease. The studies addressed long-term real-world outcomes with faricimab (Vabysmo; Genentech/Roche) in neovascular age-related macular degeneration (nAMD), a sustained-release intravitreal insert for diabetic macular edema (DME), and a novel bispecific agent targeting both VEGF and fibroblast growth factor-2 (FGF-2) in DME.

Faricimab in nAMD: Two-year real-world outcomes from 34 UK NHS sites

Raj Mukherjee, of Leeds Teaching Hospitals NHS Trust, and colleagues reported 2-year outcomes for faricimab in patients with nAMD from the FARWIDE-nAMD study, a retrospective observational study drawing on electronic health record data from 34 National Health Service (NHS) sites across the UK.¹ The overall FARWIDE-nAMD database included 22,101 patients (26,883 eyes). The 2-year cohort comprised 4,667 patients (5,582 eyes), of whom 24% were treatment-naive (TN) and 76% had previously received anti-VEGF therapy (PT).

In TN eyes, median visual acuity (VA) was 61 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline and 65 letters at 2 years. In PT eyes, median VA was 69 letters at baseline and 68 letters at 2 years. The authors described the analyses as descriptive.

Among PT eyes that had been receiving anti-VEGF therapy at intervals of 4, 6, or 8 weeks before switching to faricimab, mean injection intervals at 2 years extended to approximately 9.1, 10.0, and 11.0 weeks, respectively. The majority of PT eyes (82.9%) had switched from aflibercept 2 mg. Median injection frequency declined after the first 6 months of treatment in both TN and PT eyes. Rates of intraocular inflammation and endophthalmitis were consistent with those reported in the faricimab phase 3 trials.

The authors concluded that the FARWIDE-nAMD data reinforce the long-term real-world effectiveness, durability and safety of faricimab in nAMD, and that PT eyes previously on short treatment intervals were able to achieve meaningful interval extensions after switching.

EYP-1901 in DME: Phase 2 VERONA trial reports extended time to retreatment

Katherine E. Talcott, MD, of Cleveland Clinic, presented interim results from the VERONA trial (NCT06099184), a phase 2 study evaluating EYP-1901 (vorolanib intravitreal insert; EyePoint Pharmaceuticals) in patients with previously treated DME.² EYP-1901 is designed to deliver vorolanib, a tyrosine kinase inhibitor, continuously over at least 6 months via a bioerodible intravitreal insert. Vorolanib inhibits pan-VEGF receptor signaling and also suppresses interleukin-6 (IL-6) signalling via Janus kinase 1 (JAK1) inhibition.

VERONA enrolled 27 patients, randomized to EYP-1901 2.7 mg (n = 11), EYP-1901 1.3 mg (n = 10), or sham alongside a single aflibercept 2.0 mg injection (n = 6). All patients received aflibercept at baseline before randomisation. The primary end point was time to first supplemental anti-VEGF injection over 24 weeks. Formal statistical analysis is planned at study completion with 50 subjects; the results presented are interim and should be interpreted accordingly.

The primary end point was met. At week 24, 73% of eyes in the EYP-1901 2.7 mg arm required no supplemental anti-VEGF injection, compared with 60% in the 1.3 mg arm and 50% in the aflibercept control arm. Mean BCVA change from baseline at week 24 was +7.1, +6.9, and +7.3 ETDRS letters in the 2.7 mg, 1.3 mg, and aflibercept arms, respectively. Mean central subfield thickness (CST) reduction was −75.9 μm, −71.1 μm, and −43.7 μm, respectively. Greater reductions in macular leakage area and total macular volume were observed with both EYP-1901 doses compared with aflibercept. No EYP-1901-related safety signals were reported. EYP-1901 will be further evaluated in the phase 3 COMO (NCT06366802) and CAPRI (NCT06366815) trials.

RC28-E in DME: Bispecific FGF-2/VEGF inhibitor meets non-inferiority at 52 weeks

Youxin Chen, MD, and colleagues reported 52-week results from a phase 3 randomized controlled trial evaluating RC28-E 2.0 mg, a bispecific fusion protein designed to inhibit both VEGF-A and FGF-2, in patients with center-involved DME.³ The trial (NCT05885503) was conducted at multiple centers in China and enrolled 316 patients, randomly assigned 1:1 to RC28-E 2.0 mg or aflibercept 2.0 mg. Both groups received injections every 4 weeks for the first 16 weeks, followed by fixed 8-week dosing.

The primary end point was mean change in BCVA from baseline to week 52, with a non-inferiority margin of 4 ETDRS letters. Mean BCVA improvement was +10.6 letters in the RC28-E group and +9.8 letters in the aflibercept group, with a difference in least squares means of 0.8 letters (95% CI: −1.0 to 2.6), meeting the non-inferiority criterion. Adverse event rates were comparable between groups.

A secondary end point, the proportion of patients achieving a ≥3-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) at week 52, was 25.5% in the RC28-E group and 13.4% in the aflibercept group. Among patients with moderately severe to severe non-proliferative diabetic retinopathy at baseline, the proportion achieving ≥3-step DRSS improvement was 27.8% with RC28-E versus 11.6% with aflibercept (nominal P = .0223). The authors noted the trial was conducted in China in a predominantly homogeneous patient population, which may limit extrapolation to other populations.

Looking ahead

Taken together, the three presentations reported data on extending treatment intervals in nAMD, reducing injection burden in DME through sustained delivery, and broadening therapeutic targets in DME beyond VEGF inhibition. Results from the ongoing phase 3 COMO (NCT06366802) and CAPRI (NCT06366815) trials of EYP-1901 and other registrational programs are expected to provide further data on several of these approaches.

References

1. Mukherjee R, Varma D, Talks J, et al. Long-term effectiveness and safety of faricimab in eyes with nAMD: 2-year results from the UK FARWIDE-nAMD study. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 2850.

2. Talcott KE, Ribeiro R. VERONA phase 2 clinical trial of bioerodible EYP-1901 (vorolanib intravitreal insert) versus aflibercept for diabetic macular edema: visual, anatomic, and angiographic outcomes. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 3336.

3. Chen Y, Gu W, Sha X, et al. Intravitreal RC28-E, a recombinant fusion protein with simultaneous inhibition of fibroblast growth factor-2 and vascular endothelial growth factor in patients with diabetic macular edema: 52-week results from a randomized, double-masked, phase 3 trial. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 3337.