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Diabetic Macular Edema and the VERONA Trial

Next-generation therapy aims to cut injection frequency while maintaining vision in diabetic macular edema

By Christiana Dinah, Adrienne W. Scott 10/22/2025 5 min read

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Adrienne W. Scott (left) and Christiana Dinah
Severe, sight-threatening diabetic retinopathy consists of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). DME is a leading cause of blindness in working-age adults worldwide (1). Vision loss can develop from any stage of DR, but incidence increases with more advanced DR stages (2,3). Chronic hyperglycemia can cause DME through the build-up of glycated molecules that break down the blood-retina barrier, resulting in the accumulation of fluid under and within the retina (4,5). Additionally, the upregulation of several pathways, such as inflammatory cytokines (IL-6) and vascular endothelial growth factor (VEGF), leads to inflammation, oxidative stress, and overall vascular dysfunction (5).

Several treatment approaches are used to control DME, most commonly intravitreal anti-VEGF therapy as first-line agents (6), with intravitreal corticosteroids and laser photocoagulation used in select cases (7). Anti-VEGF therapy has been shown to effectively control DME disease activity and maintain vision (7). While steroids improve vision by reducing inflammation, and thus decreasing vascular leakage and macular thickness, they can be associated with adverse events including increased intraocular pressure and cataract progression (7).

In community practice, vision outcomes with anti-VEGF therapy do not match those observed in clinical trial as vision gains may not be maintained long-term (8,9). One possible reason for this disparity is the associated treatment burden (10), as some treatment schedules require injections as often as every 4 to 8 weeks (11, 12) and potentially require additional visits for disease monitoring. This burden may lead to missed visits, which can result in suboptimal vision outcomes (9). Patients may also miss treatments due to chronic comorbidities, which may be due to complications of their diabetes (13, 14). Additionally, frequent visits can result in absenteeism at work, a concern since many DME patients are of working age (10,15). With its prevalence expected to increase 45% worldwide from 2024 to 2050 (16), management of diabetes and its complications is a growing concern. For DME specifically, treatments that meaningfully extend treatment interval to reduce burden while preserving vision are of great interest.

One treatment under investigation is DURAVYUTM* (vorolanib intravitreal insert), a bioerodible sustained-release insert administered intravitreally. DURAVYU uses next-generation Durasert E™ drug delivery technology to deliver a daily therapeutic dose of the tyrosine kinase inhibitor (TKI) vorolanib for at least six months (17). Vorolanib provides a novel mechanism of action (MOA) by functioning intracellularly to inhibit all three VEGF receptors (VEGF-R), unlike anti-VEGF monotherapy which inhibits VEGF-A/B ligands extracellularly (18). Unlike other TKIs, vorolanib does not inhibit the TIE2 receptor whose activation has a role in vascular stabilization (18). Durasert E™ is designed to prevent free-floating drug particles in the vitreous and does not contain polyethylene glycol (PEG) or poly(lactic-co-glycolic) acid (PLGA) (19). DURAVYU has completed phase II trials for both neovascular age-related macular degeneration (nAMD) (20) and DME (21), and is currently being evaluated in phase III trials for nAMD with a 6-month redosing schedule (22).

The VERONA trial

The phase II VERONA (NCT06099184) trial assessed the efficacy, durability, and safety of a single injection of DURAVYU versus aflibercept in patients with active DME. On day one, patients received a single injection of aflibercept 2.0 mg followed by an injection of DURAVYU 1.3 mg, DURAVYU 2.7 mg, or sham (aflibercept arm) 30 minutes later. Beginning at week 4, all patients were evaluated for supplemental aflibercept 2.0 mg treatment based on prespecified BCVA and/or anatomic criteria, or per Investigator’s discretion. Patients were evaluated every four weeks for 24 weeks. The primary endpoint was time to first supplemental anti-VEGF injection (23).

Twenty-seven patients were enrolled in VERONA (DURAVYU 1.3 mg, n = 10; DURAVYU 2.7 mg, n = 11; aflibercept, n = 6). Baseline characteristics were well-balanced across arms. Patients had received an average of 2.7 anti-VEGF injections in the year prior to study enrollment. VERONA met its primary endpoint; both dose levels of DURAVYU achieved extended time to first supplemental treatment vs aflibercept anti-VEGF monotherapy alone. Up to W24, the majority of DURAVYU patients were supplement-free with 60% of DURAVYU 1.3 mg patients and 73% of DURAVYU 2.7 mg patients supplement-free versus 50% in the aflibercept arm (23).

Following a single dose of DURAVYU, clinically meaningful improvements in BCVA were observed as early as W4 and sustained through W24 with mean change from baseline of +6.9, +7.1, and +7.3 letters with DURAVYU 1.3 mg, 2.7 mg, and aflibercept, respectively. BCVA gains were observed at W4, the first post-treatment visit, suggesting early drug bioavailability with DURAVYU. Further, when a single outlier patient who missed multiple visits was excluded, BCVA in the DURAVYU 2.7 mg arm improved +10 letters from baseline. Similar clinically meaningful improvements with early bioavailability were observed in central subfield thickness (CST). At W24, CST decreased −71.1 µm and −75.9 µm in the DURAVYU 1.3 mg and 2.7 mg arms versus −43.7 µm in the aflibercept arm. Improvements with DURAVYU over aflibercept were also observed at W4.

In a subgroup analysis of eyes that were supplement-free for the entire study, both dose levels of DURAVYU demonstrated better BCVA outcomes after a single injection versus aflibercept. BCVA change from baseline at W24 was +6.5 and +10.3 letters in the DURAVYU 1.3 mg and 2.7 mg arms versus +3.0 letters with aflibercept. In the same patients, better anatomic control was also observed with DURAVYU 2.7 mg compared with aflibercept with mean CST change from baseline of −117.4 µm versus −43.7 µm, respectively.

DURAVYU was well-tolerated with no DURAVYU-related ocular or systemic serious adverse events reported in VERONA and no safety signals. There were no cases of endophthalmitis, retinal vasculitis (occlusive or non-occlusive), intraocular inflammation, insert migration into the anterior chamber, or discontinuations due to adverse events. These safety results align with other DURAVYU trials in nAMD and DR, suggesting an overall favorable safety profile across multiple indications with over 190 patients evaluated.

Altogether, these efficacy and safety data support DURAVYU’s potential to provide durable DME control. Notably, even as early as the first post-treatment visit, vision gains with both DURAVYU and aflibercept were greater than those achieved with aflibercept alone, suggesting that there may be synergistic clinical benefit from the dual MOAs provided by the two drugs. Additionally, sustained vision and anatomic improvements were observed with over 70% of DURAVYU 2.7 mg-treated patients remaining supplement-free up to 24 weeks after treatment, suggesting the potential for DURAVYU to decrease treatment burden for DME patients. This is of particular importance for patients with DME, who have expressed the negative impact of frequent intravitreal injections on both their employment and their mental health (10, 24). Unsurprisingly, the burden of treatment has been shown to contribute to missed appointments, which can contribute to worse clinical outcomes (9, 14).

With its novel MOA and sustained release technology, DURAVYU may be a treatment option that allows patients living with this chronic disease to go longer between visits while maintaining DME and optimizing their visual outcomes.

*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 US and Marketing Authorization in any other country and the timeline for potential approval or authorization is uncertain.  

References

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About the Author(s)

Christiana Dinah

Christiana Dinah is the Director of Research and Development and a Consultant Ophthalmologist at the London North West University Healthcare NHS Trust. Financial disclosures: Institutional grants: Apellis, Roche, Topcon; Advisory boards and consulting: AbbVie, Alimera Sciences, Apellis, Astellas, Bayer, Boehringer Ingelheim, EyePoint, Johnson and Johnson, Ocular Therapeutics, Roche; Speaker fee: AbbVie, Apellis, Bayer, Boehringer Ingelheim, Roche, Topcon

More Articles by Christiana Dinah

Adrienne W. Scott

Adrienne W. Scott is the Fred M. Leader Family Retina Professor of Ophthalmology at the Wilmer Eye Institute at Johns Hopkins Medicine.

More Articles by Adrienne W. Scott

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