VERONA Meets Primary Endpoint of Time to Supplement in DME, with Yasha Modi, MD

The recent phase 2 VERONA study has achieved its primary endpoint of EYP-1901 achieving extended time to first supplemental treatment versus aflibercept in diabetic macular edema (DME), according to a presentation at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA.1

Presented by Yasha Modi, MD, New York University, VERONA assessed the efficacy, durability, and safety of 1 intravitreal injection of EYP-1901, a sustained-release tyrosine kinase inhibitor insert, versus aflibercept in DME. Modi and colleagues cited a significant unmet need for durable treatment options for DME which can maintain disease control while reducing injection frequency.1

Recent research has opened the floodgates of treatment extension across ophthalmology. In the DME sphere, a long history of reliance on anti-VEGF therapies and the repeated injections they require have led to a surge of research concerning medications that allow longer time between treatments. Additionally, DME treatment burden is heavily skewed towards early treatment, presenting a unique consideration than other ophthalmic diseases.2

The randomized, open-label clinical trial included patients with DME who were previously treated with a standard-of-care anti-VEGF therapy. All included patients were randomized to an injection of aflibercept 2mg followed by a single injection of either EYP-1901 2.7mg, EYP-1901 1.3mg, or sham. Investigators followed patients monthly for 24 weeks; at each visit, patients were assessed for supplemental anti-VEGF treatment per prespecified best-corrected visual acuity (BCVA) and anatomical criteria or per the investigators’ discretion.1

Aside from the primary endpoint of time to supplemental anti-VEGF injection up to week 24, secondary endpoints included mean change in BCVA, central subfield thickness (CST), and safety through week 24.1

A total of 27 patients were initially enrolled; 11 were assigned to EYP-1901 2.7mg, 10 to EYP-1901 1.3mg, and 6 to aflibercept 2mg. No discontinuations occurred during the trial, and VERONA met its primary endpoint with both EYP-1901 doses achieving extended time to first supplemental injection versus aflibercept. EYP-1901 2.7mg displayed early and sustained BCVA and CST improvement, with effects first seen at week 4, the first post-treatment visit.1

Week 24 saw a mean BCVA change from baseline of +7.1, +6.9, and +7.3 letters in the EYP-1901 2.7mg, 1.3mg, and aflibercept arms, respectively. Mean CST change from baseline was -75.9 µm, -71.1µm, and -43.7 µm, respectively. The proportion of supplement-free eyes by week 24 was 73%, 60%, and 50%, respectively. The 2.7mg arm also saw a reduction in treatment burden of >2/3. No ocular or systemic serious adverse events were reported.1

Modi sat down with HCPLive to discuss the structure, results, and applications of VERONA, highlighting the treatment ceiling for visual acuity gains, the importance of minimizing injections for patients, and the value in larger, longer-scale studies to track down potential negative outcomes.

“What we’re starting to realize is that we’re kind of getting to the ceiling effect, where all of our therapeutics really can have excellent visual acuity gains,” Modi told HCPLive. “But relative to one another, they’re all about the same. So if you’re using bevacizumab versus aflibercept versus faricimab, your visual acuity tends to max out at that ceiling level.”

Modi went on to note the actual goals of patients entering these studies – or simply presenting with DME. Given the previously mentioned treatment ceiling, extending dose intervals is quickly becoming the target for many ongoing and future clinical trials.

“Patients really want two things. They want fewer injections, and they want to spend less time with us in the clinic,” Modi said. “And so all therapeutics are really designed now to try and increase that durability. The entire premise of the TKIs as a platform is to see if we can extend that time between injections out to that sort of six-month window.”

Editor's Note: Modi reports disclosures with Neurotech, Zeiss, Genentech, Eyepoint, DORC, Abbvie/Allergen, and others.

References

1. Modi Y, Almeida D, Khanani A, Danzig C, Ribeiro R. VERONA: End-of-Study Results From a Phase 2 Trial of EYP-1901 (Vorolanib Intravitreal Insert) vs Aflibercept for Diabetic Macular Edema. Abstract presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists, Long Beach, CA, July 30-August 2, 2025.

2. Subhi Y, Potapenko I, Hajari JN, la Cour M. Anti-VEGF Treatment of Diabetic Macular Edema in Denmark: Incidence, Burden of Therapy, and Forecasting Analyses. J Pers Med. 2023;13(3):546. Published 2023 Mar 18. doi:10.3390/jpm13030546