Despite the availability of anti-vascular endothelial growth factor (VEGF) therapies for wet age-related macular degeneration (AMD) and diabetic macular edema (DME), treatment burden remains high, often leading to undertreatment and long-term vision loss (1-5), highlighting the need for durable therapies that provide continuous disease control and address the multifactorial pathophysiology of retinal disease.

EYP-1901 (vorolanib intravitreal insert; DURAVYU™)* offers sustained release of the tyrosine kinase inhibitor (TKI) vorolanib via next-generation bioerodible Durasert E™ technology, delivering therapeutic levels for at least six months following a single intravitreal injection (6). EYP-1901 is being evaluated in a robust clinical trial program, including completed phase 1 and 2 trials, and ongoing pivotal phase 3 trials (7-13).

The phase 3 LUGANO (NCT06668064) and LUCIA (NCT06683742) trials in wet AMD and the COMO (NCT07449936) and CAPRI (NCT07449923) trials in DME are evaluating EYP-1901 2.7 mg administered every six months versus on-label aflibercept 2 mg every eight weeks (q8W) in treatment-naïve and previously treated patients (14). Across the trials, the primary endpoint is the average change in best-corrected visual acuity (BCVA) from Day 1 to Week 52/56 (14). Topline data are anticipated in mid-2026 for LUGANO, shortly thereafter for LUCIA (14, 15). Enrollment completion for COMO and CAPRI is anticipated in Q3 2026, with topline data anticipated in Q4 2027 (14, 15).

Unlike anti-VEGF therapies that work extracellularly to bind VEGF ligands, vorolanib acts intracellularly to suppress angiogenesis through inhibition of pan-VEGF receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) signaling (16). In addition to its anti-angiogenic activity, vorolanib offers a multi-MOA by inhibiting interleukin-6 (IL-6)-mediated inflammatory signaling through interaction with the kinase JAK1 (Figure 1) (17).

Nonclinical data supporting IL-6 inhibition were presented by Dr. Sumit Sharma, MD (Cole Eye Institute, Cleveland Clinic, Cleveland, OH) (18). A high-sensitivity, gold-standard (19) radiometric kinase discovery screen identified vorolanib as a potential strong inhibitor of JAK1. In follow-up analyses, vorolanib exhibited a lower IC₅₀ for JAK1 compared with other tested TKIs (sunitinib, axitinib), indicating stronger inhibition and supporting primary screen findings. A proof-of-concept luciferase assay demonstrated that vorolanib inhibits IL-6 activity with a dose-dependent response. Additionally, in a cell-based TEER assay, vorolanib maintained cell membrane integrity to a similar extent as anti-VEGF and anti-IL-6 combined, suggesting potential to reduce vascular leakage (18).

Figure 1. Vorolanib multi-mechanism of action.
Vorolanib binds intracellularly to VEGFR-1, -2, and-3 and PDGFR to inhibit downstream angiogenic signaling, and also inhibits inflammatory IL-6 signaling via interaction with the kinase JAK1.
Figure reproduced with permission from Sharma S, Lynch J, Sellos-Moura M. Multi-Mechanism of Action of EYP-1901 in Retinal Exudative Diseases: Inhibition of IL-6 Signaling, VEGFR and PDGFR by Vorolanib. Presented at: American Society of Retina Specialists Annual Meeting, July 15–18, 2026; Montréal, Canada.

Key learnings from the phase 2 DAVIO 2 trial (NCT05381948) were presented by Dr. Avni P. Finn, MD, MBA, FASRS (Vanderbilt Eye Institute, Nashville, TN) (20). DAVIO 2 enrolled 161 patients with previously-treated wet AMD and baseline best-corrected visual acuity (BCVA) 35-85 letters, who were randomized to receive a single dose of EYP-1901 2 mg, EYP-1901 3 mg, or on-label aflibercept 2 mg every eight weeks (q8W). DAVIO 2 met its primary endpoint; mean change in BCVA from baseline with a single dose of EYP-1901 2 mg or 3 mg was statistically noninferior to aflibercept 2 mg q8W. Stable anatomical control was seen with EYP-1901, with no sawtooth fluctuations in CST as observed in the aflibercept 2 mg q8W arm. Stable (<5-letter change) or improved (≥5-letter gain) vision was observed in over 85% of EYP-1901-treated patients 6 months after administration. Notably, no EYP-1901–treated eyes had loss ≥15 letters. A time-in-range analysis demonstrated that a single EYP-1901 3 mg injection maintained vision ≥69 letters (~20/40 Snellen equivalent, minimum driving requirement in most US states) for 28 of 32 weeks. EYP-1901-treated patients demonstrated an ≥85% overall reduction in treatment burden versus pre-trial. There were no EYP-1901-related ocular or systemic serious adverse events observed (20).

Findings from a DAVIO 2 post hoc analysis investigating visual, anatomic, and supplemental treatment outcomes in patients who met LUGANO/LUCIA criteria for baseline vision (baseline BCVA eligibility in LUGANO and LUCIA was slightly narrower than in DAVIO 2 [35-78 letters vs 35-85 letters, respectively]) and for supplemental treatment (Figure 2) were presented by Dr. Aleksandra Rachitskaya, MD (Cole Eye Institute, Cleveland Clinic, Cleveland, OH) (21). In the subgroup of DAVIO 2 patients with baseline BCVA 35-78 letters, vision and CST were stable across arms. When applying the LUGANO/LUCIA supplemental treatment criteria, fewer EYP-1901 3 mg-treated patients in DAVIO 2 met the protocol-defined criteria for supplementation (21).

Figure 2. Supplemental treatment criteria in the DAVIO 2, LUGANO, and LUCIA trials.
Patients were evaluated for eligibility to receive supplemental aflibercept treatment based on prespecified criteria. The criteria for the phase 2 DAVIO 2 trial and the phase 3 LUGANO and LUCIA trials are listed here. ^a Due to wet AMD; from best on-study measurement.
Figure reproduced with permission from Rachitskaya A, Ribeiro R. DAVIO 2 Phase 2 Trial of Bioerodible EYP-1901 (vorolanib intravitreal insert) in Wet AMD: Post Hoc Analysis in Patients Who Met Phase 3 Trial Criteria. Presented at: American Society of Retina Specialists Annual Meeting, July 15–18, 2026; Montréal, Canada.

Yasha S. Modi, MD (Northwell Health, Manhattan, Eye, Ear and Throat Hospital, New York, NY) presented results from the phase 2 VERONA trial (NCT06099184), which enrolled 27 previously-treated patients with active DME (22). Patients received a single dose of aflibercept 2 mg followed by a single dose of EYP-1901 1.3 mg, 2.7 mg, or sham. VERONA met its primary endpoint; both EYP-1901 dose levels extended time to first supplemental treatment versus aflibercept 2 mg. A higher proportion of patients were supplement-free up to Week 24 with EYP-1901 2.7 mg (73%) compared to aflibercept 2 mg (50%). Early and sustained vision and anatomic improvements were observed with a single EYP-1901 dose. At Week 24, mean BCVA change from baseline were +6.9, +7.1, and +7.3 letters, and mean CST change from baseline were −71.1, −75.9, and −43.7 µm with EYP-1901 1.3 mg, EYP-1901 2.7 mg, and aflibercept 2 mg, respectively. Dose-dependent reductions in macular volume and macular leakage area were observed in the EYP-1901 1.3 mg and EYP-1901 2.7 mg arms (22).

Across 4 completed phase 1 and 2 trials to date, in over 190 patients, EYP-1901 has been found to be well-tolerated, with no EYP-1901 drug-related safety concerns and no EYP-1901-related discontinuations (14). Based on interim masked safety data (all treatment arms), the observed safety profile in LUGANO/LUCIA is consistent with previous EYP-1901 clinical trials (23).

A robust clinical development program supports the potential of EYP-1901 to improve long-term visual outcomes and reduce treatment burden in patients with wet AMD and DME.

*DURAVYU™ has been conditionally accepted by the US FDA as the proprietary name for
EYP-1901 (vorolanib intravitreal insert). EYP-1901 is an investigational medicinal product and is not authorized for sale in any country at the time of this publication. FDA approval in the US and Marketing Authorization in any other country and the timeline for potential approval or authorization is uncertain. The dose investigated in phase 3 trials is 2.686 mg (two inserts of 1.343 mg each) administered in a single injection. Results from the post hoc DAVIO 2 analysis are not predictive of phase 3 results.