EyePoint’s DURAVYU failed non-inferiority in the LUCIA Phase 3 wet AMD trial despite a 38% lower treatment burden, shifting focus to DME.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
EyePoint’s investigational sustained-release therapy DURAVYU (vorolanib intravitreal insert) failed to demonstrate statistical non-inferiority to aflibercept in the Phase 3 LUCIA trial for wet age-related macular degeneration (AMD). Although the treatment reduced supplemental injection requirements, visual acuity gains were lower than with aflibercept, leaving the therapy’s future in wet AMD uncertain as the company prioritizes its diabetic macular edema (DME) program.
LUCIA Misses Primary Visual Acuity Endpoint
LUCIA enrolled 475 patients with wet AMD and compared DURAVYU 2.7 mg administered every 24 weeks with on-label aflibercept 2 mg every eight weeks, following three monthly loading doses. Both groups could receive supplemental aflibercept injections according to prespecified criteria.
At the blended Weeks 52 and 56 assessment, DURAVYU-treated eyes gained a least-squares mean of 2.5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, compared with 6.1 letters in the aflibercept arm. The reported between-group difference was −3.7 letters. The confidence interval extended beyond the prespecified non-inferiority margin of −4.5 letters, meaning the trial failed its primary endpoint. These topline figures remain preliminary, pending final analysis.
Despite this result, LUCIA met key secondary endpoints. DURAVYU reduced treatment burden by 38% compared with aflibercept, with a nominal p-value below 0.0001. By Week 56, 52% of treated eyes remained free of supplemental aflibercept, while 71% received zero or one supplemental injection. The company also reported strong anatomical control and a favorable safety profile with repeat dosing.
Second Phase 3 Failure Complicates Wet AMD Development
The findings follow LUGANO, which enrolled 432 patients and also failed to meet its primary non-inferiority endpoint in the full analysis population. Although an exploratory analysis excluding nine DURAVYU-treated patients with substantial vision loss attributed to causes unrelated to wet AMD met the non-inferiority criterion, this did not change the outcome in the full dataset. LUGANO reported a 42% reduction in treatment burden.
Failure to meet the primary endpoint in both pivotal trials substantially weakens DURAVYU’s current regulatory case in wet AMD. The results do not establish non-inferiority to standard aflibercept treatment, and further analyses alone would not guarantee an acceptable basis for FDA approval. EyePoint has said it will analyze the LUCIA and pooled Phase 3 datasets to assess the remaining options for the indication.
Sustained-Release Technology and Mechanism
DURAVYU combines vorolanib, an investigational tyrosine kinase inhibitor, with EyePoint’s bioerodible Durasert E delivery platform, which releases the drug over at least six months.
Vorolanib inhibits VEGF receptors and platelet-derived growth factor receptors (PDGFR), targeting intracellular pathways involved in angiogenesis. It also inhibits interleukin-6 (IL-6)/JAK1 signaling, providing a potential additional anti-inflammatory mechanism beyond extracellular VEGF blockade.
The LUCIA announcement reported a favorable safety profile with redosing. However, detailed comparative adverse-event rates were not included in the topline release, limiting assessment of the full benefit-risk profile.
DME Program Remains the Development Priority
EyePoint is continuing its pivotal Phase 3 COMO and CAPRI trials in DME, with topline results expected in the fourth quarter of 2027.
The program follows the Phase 2 VERONA trial, which met its primary endpoint by extending the time to first supplemental injection compared with aflibercept for both DURAVYU doses. At Week 24, the 2.7 mg dose produced a mean BCVA gain of 7.1 letters and a 76-micron reduction in central subfield thickness. The supplement-free rate was 73%, compared with 50% in the control arm. No DURAVYU-related ocular or systemic serious adverse events were reported.
Clinical Interpretation
The two wet AMD trials illustrate the distinction between reducing injection frequency and maintaining visual outcomes comparable to established treatment. DME provides a separate biological rationale for investigation because diabetic retinal disease involves interacting vascular and inflammatory pathways, including IL-6 signaling. However, this mechanism does not establish that DURAVYU will perform better in DME. The ongoing Phase 3 trials will determine whether the encouraging Phase 2 findings translate into sustained visual outcomes with fewer supplemental injections.
Reference
EyePoint Announces Topline Results from LUCIA, the Second Pivotal Phase 3 Clinical Trial of DURAVYU™ in Wet AMD, Eyepoint, 19 October 2026
A 2-year Study of EYP-1901 in Subjects with Wet Age-Related Macular Degeneration (wAMD) (LUCIA) Primary Efficacy Will be Determined at Week 56 (wAMD), ClinicalTrials.gov ID NCT06683742
A 2-year Study of EYP-1901 in Subjects with Wet Age-Related Macular Degeneration (wAMD) (LUGANO) Primary Efficacy Will be Determined at Week 56 (wAMD), ClinicalTrials.gov ID NCT06668064
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.