A look at the vorolanib intravitreal insert compared with aflibercept for DME

(Image credit: AdobeStock/photon_photo)

First-time results of the phase 2 VERONA (NCT06099184) trial of the vorolanib intravitreal insert known as EYP-1901 (Duravyu; EyePoint) for diabetic macular edema (DME) were presented at the Retina World Congress 2025 in Fort Lauderdale, Florida. ¹

EYP-1901, in development for DME and neovascular age-related macular degeneration (nAMD), is a bioerodible intravitreal insert using Durasert-E^TM drug delivery technology to provide sustained release of vorolanib for at least 6 months. ^2-4 Vorolanib is a potent and selective tyrosine kinase inhibitor (TKI) that acts intracellularly to inhibit VEGF receptor signaling, thereby inhibiting angiogenesis and exudation. ²

Durasert-E, an intravitreal insert, is the next-generation, bioerodible version of Durasert, which has been used in 4 FDA-approved products to date to provide sustained intraocular drug delivery. ^4-7

VERONA is a phase 2, randomized, controlled clinical trial of EYP-1901 vs aflibercept in patients with center-involved DME previously treated with at least 1 anti-VEGF injection. It is the only clinical trial to date designed to assess the safety and efficacy of a tyrosine kinase inhibitor in patients with DME.

In VERONA, patients with active DME received a single injection of aflibercept 2.0 mg and either EYP-1901 2.7 mg (n=11), EYP-1901 1.3 mg (n=10), or sham (n=6; aflibercept arm), and were assessed every 4 weeks thereafter through week 24 for supplemental aflibercept 2.0-mg injections using prespecified criteria: best-corrected visual acuity (BCVA) reduction 5 to 9 letters and central subfield thickness (CST) increase of more than 75 µm on 2 consecutive visits; or BCVA reduction of 10 or more letters due to DME; or CST increase of 100 µm or more vs baseline; or investigator discretion. Additionally, starting at week 12, patients could receive supplemental aflibercept if they did not have a 10% reduction in CST vs baseline. The primary end point was the time to first supplemental anti-VEGF injection; secondary end points included safety, mean BCVA change from baseline, and mean CST change from baseline.

At baseline, patients’ BCVA averaged an Early Treatment Diabetic Retinopathy Study letter score of 66 to 67 (~20/50 Snellen equivalent) across arms, with mean CST of 430.1, 395.5, and 392.3 μm in the EYP-1901 2.7-mg, EYP-1901 1.3-mg, and aflibercept arms, respectively. No patients discontinued the trial.

VERONA met its primary end point. Up to week 24, 73% and 60% of patients treated with EYP-1901 2.7 mg and 1.3 mg were supplement free, vs 50% of the aflibercept arm patients. Through the end of the trial, 64%, 60%, and 50% of patients, respectively, remained supplement free.

Patients treated with EYP-1901 2.7 mg had early and sustained improvements in both BCVA (mean, +7.0 letters from baseline at week 4) and CST (mean, −90.3 μm from baseline at week 4), with the beneficial effects considerably greater than aflibercept alone (mean, BCVA: +2.2 letters; CST: −38.8 μm) evident at week 4, indicating immediate bioavailability of vorolanib with EYP-1901. BCVA gains from baseline were overall similar across arms at week 24 (EYP-1901 2.7 mg, +7.1; EYP-1901 1.3 mg, +6.9; aflibercept alone, +7.3 letters). One outlier patient in the EYP-1901 2.7-mg arm missed multiple visits; excluding this patient, mean BCVA gains in the EYP-1901 2.7-mg arm were +10.1 letters from baseline at week 24. Similarly, CST decreased with Duravyu, particularly in the 2.7-mg arm, which averaged a −75.9-µm change from baseline at week 24 compared with −43.7 µm from baseline in the aflibercept arm.

In a subgroup analysis of eyes that were supplement free for the entire study, Duravyu 2.7 mg demonstrated better BCVA (mean, +10.3 letters) and better anatomic outcomes (mean, −117.4 μm) vs the aflibercept control (BCVA, +3.0 letters; CST, −43.7 μm). Further, 43% of supplement-free patients in the Duravyu 2.7-mg arm had an absence of DME at week 24 compared with 0% in the aflibercept arm.

EYP-1901 demonstrated a favorable safety profile, with no ocular or systemic serious adverse events (SAEs) related to EYP-1901. Furthermore, there were no cases of endophthalmitis, retinal vasculitis (occlusive or nonocclusive), intraocular inflammation, or insert migration into the anterior chamber. Across EYP-1901 clinical trials, no EYP-1901–related ocular or systemic SAEs have been reported to date, further strengthening the safety profile of EYP-1901.

Overall, in VERONA, EYP-1901 provided immediate and clinically meaningful improvements in BCVA and CST. These results were observed with a meaningful reduction in treatment burden. Together, these data support further investigation of EYP-1901 as a potential treatment for DME.

Conclusion

EYP-1901 has the potential to substantially reduce treatment burden for DME relative to current intravitreal therapeutics targeting VEGF, while being delivered in-office via a standard intravitreal injection. Furthermore, EYP-1901 releases vorolanib continuously, ensuring active drug is present from the day of administration through at least 6 months.

The FDA has conditionally accepted Duravyu as the proprietary name for EYP-1901. Duravyu is an investigational product; the FDA has not approved it. FDA approval and the timeline for potential approval are uncertain.

Disclosure: Carl Regillo, MD, is a consultant for EyePoint Pharmaceuticals, Inc.

References

1.Regillo CD. VERONA: Results from a phase 2 trial of EYP-1901 (vorolanib intravitreal insert) versus aflibercept for diabetic macular edema. Presented at: Retina World Congress 2025; May 8-11, 2025; Fort Lauderdale, FL.

2.Bakri SJ, Lynch J, Howard-Sparks M, Saint-Juste S, Saim S. Vorolanib, sunitinib, and axitinib: a comparative study of vascular endothelial growth factor receptor inhibitors and their anti-angiogenic effects. PLoS One. 2024;19(6):e0304782. doi:10.1371/journal.pone.0304782

3.Patel S, Storey PP, Barakat MR, et al. Phase I DAVIO trial: EYP-1901 bioerodible, sustained-delivery vorolanib insert in patients with wet age-related macular degeneration. Ophthalmol Sci. 2024;4(5):100527. doi:10.1016/j.xops.2024.100527

4.Wykoff CC, Kuppermann BD, Regillo CD, et al. Extended intraocular drug-delivery platforms for the treatment of retinal and choroidal diseases. J Vitreoretin Dis. 2024;8(5):577-586. doi:10.1177/24741264241267065

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6.Yutiq. Prescribing information. Alimera Sciences; 2023. https://yutiq.com/wp-content/uploads/2025/02/YUTIQ-PI-June-2023.pdf

7.Retisert. Prescribing information. Bausch + Lomb; 2025. https://www.bausch.com/globalassets/pdf/packageinserts/pharma/retisert-prescribing-information.pdf