Duravyu misses wet AMD end point again as EyePoint pivots to DME

EyePoint said it will end its 2 phase 3 trials of Duravyu (vorolanib intravitreal insert) in neovascular age-related macular degeneration (nAMD) early and focus on diabetic macular edema (DME). The decision follows topline results from LUCIA, the second of the 2 trials, which did not meet its primary end point.¹ The company plans to cut about 53% of its workforce and stop the wet AMD trials before the second year of each is finished. Pivotal DME data are expected in the fourth quarter of 2027.¹

For retina specialists, this means neither phase 3 trial of the sustained-release tyrosine kinase inhibitor (TKI) insert showed noninferior visual acuity vs on-label aflibercept in its full dataset. The program's near-term value to clinicians now rests on whether the insert's durability signal holds up in DME.

LUCIA and LUGANO results

LUCIA (475 patients) and LUGANO (432 patients) were identical, randomized, double-masked, aflibercept-controlled noninferiority trials in treatment-naive and previously treated patients with active wet AMD. After 3 monthly loading doses, patients were randomly assigned 1:1 to Duravyu 2.7 mg every 6 months or aflibercept 2 mg every 8 weeks, with supplemental aflibercept given according to prespecified criteria. The primary end point was mean change in best-corrected visual acuity (BCVA) from baseline, averaged across weeks 52 and 56.^2-6

In LUCIA, Duravyu did not achieve statistical noninferiority in BCVA, although the company reported visual improvement. Treatment burden was 38% lower than with control (nominal P < .001). Through week 56, 52% of Duravyu eyes needed no supplemental injection and 71% needed no more than 1.² The company did not report mean letter changes, the treatment difference, its confidence interval, or the noninferiority margin in the topline release.

LUGANO, reported in August, also missed its primary end point. The company attributed the miss to 9 patients (about 4%), unevenly distributed between arms, who lost vision for reasons other than wet AMD. A post hoc analysis excluding these patients showed noninferiority. Treatment burden was 42% lower, and 76% and 54% of Duravyu patients were supplement-free through weeks 32 and 56, respectively.^3,4 Post hoc exclusions cannot replace the prespecified analysis, and the replicate trial has now also missed the end point.

The company said Duravyu remained safe with redosing in both trials. It reported no drug-related safety concerns in more than 630 patients across 6 completed trials.² Detailed adverse event tables have not yet been released.

Clinical context

A meta-analysis estimated that 18.83 million adults worldwide had clinically significant macular edema in 2020, projected to rise to 28.61 million by 2045.⁷ Intravitreal anti-VEGF therapy is the standard of care for center-involved DME. In the DRCR Retina Network Protocol T trial, aflibercept, bevacizumab, and ranibizumab all improved vision at 1 year, but the relative benefit depended on baseline acuity.⁸ Frequent injections remain a barrier to adherence, which is the gap sustained-delivery platforms aim to fill.

Drug background

Duravyu pairs vorolanib with EyePoint's bioerodible Durasert E insert, which is designed to release drug for at least 6 months. Vorolanib is a pan-VEGF receptor TKI derived from sunitinib. Preclinical work suggests it has a shorter half-life and less tissue accumulation than other TKIs.⁹ The company also says vorolanib inhibits PDGFR and IL-6/JAK1 signaling, but these anti-inflammatory claims come from EyePoint and have not been independently confirmed in clinical studies. The phase 1 DAVIO trial in nAMD was published in Ophthalmology Science in 2024.¹⁰

The DME rationale rests mainly on the phase 2 VERONA trial.¹¹ VERONA enrolled 27 patients who had previously received anti-VEGF therapy. They were randomly assigned to Duravyu 1.3 mg, Duravyu 2.7 mg, or aflibercept.¹² The trial met its primary end point, longer time to first supplemental injection with both doses. At week 24, the 2.7-mg dose produced a gain of 7.1 letters and a 76-µm reduction in central subfield thickness, and 73% of patients were supplement-free vs 50% of controls.²

Interpretation

EyePoint CEO Jay S. Duker, MD, said the wet AMD findings support Duravyu's potential in DME, pointing to the disease's inflammatory component and the VERONA results.² That reasoning is plausible, but it has not been tested. VERONA was a small phase 2 trial with 24-week primary data. The wet AMD trials consistently reduced injection burden, but in both trials that reduction came without demonstrated noninferior visual acuity, which is the outcome regulators and clinicians weigh most.

Limitations and next steps

The LUCIA results are topline, and no peer-reviewed publications exist for either phase 3 trial. EyePoint said it will analyze the LUCIA data and the pooled phase 3 data further before deciding next steps in wet AMD.² The company did not say whether it still plans the new drug application it had previously targeted for the first half of 2027.³

COMO and CAPRI enrolled 551 patients, about 75% of them treatment-naive. Patients were randomly assigned 1:1 to Duravyu 2.7 mg every 6 months or aflibercept every 8 weeks. The primary end point is the same BCVA noninferiority measure used in the wet AMD trials. EyePoint reported about $118 million in cash and investments as of September 30, 2026, and expects the restructuring to save about $30 million a year, with one-time charges of about $9 million.^1,13,14

References

1. EyePoint announces strategic prioritization. News release. EyePoint, Inc. October 19, 2026. https://investors.eyepoint.bio/news-releases/news-release-details/eyepoint-announces-strategic-prioritization

2. EyePoint announces topline results from LUCIA, the second pivotal phase 3 clinical trial of Duravyu in wet AMD. News release. EyePoint, Inc. October 19, 2026. https://www.globenewswire.com/news-release/2026/10/19/3383257/0/en/eyepoint-announces-topline-results-from-lucia-the-second-pivotal-phase-3-clinical-trial-of-duravyu-in-wet-amd.html

3. EyePoint announces topline data from LUGANO, the first of two pivotal phase 3 clinical trials for Duravyu 2.7 mg in wet AMD. News release. EyePoint, Inc. August 17, 2026. https://investors.eyepoint.bio/node/20086

4. Interpreting the LUGANO trial. Retinal Physician. July/August 2026. https://retinalphysician.com/issues/2026/july-august/interpreting-the-lugano-trial

5. LUGANO. ClinicalTrials.gov identifier: NCT06668064. https://clinicaltrials.gov/study/NCT06668064

6. LUCIA. ClinicalTrials.gov identifier: NCT06683742. https://clinicaltrials.gov/study/NCT06683742

7. Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580-1591. doi:10.1016/j.ophtha.2021.04.027. https://doi.org/10.1016/j.ophtha.2021.04.027

8. Wells JA, Glassman AR, Ayala AR, et al; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193-1203. doi:10.1056/NEJMoa1414264. https://doi.org/10.1056/NEJMoa1414264

9. 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. https://doi.org/10.1371/journal.pone.0304782

10. 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. https://doi.org/10.1016/j.xops.2024.100527

11. VERONA. ClinicalTrials.gov identifier: NCT06099184. https://clinicaltrials.gov/study/NCT06099184

12. Comparing vorolanib intravitreal insert with aflibercept in DME treatment. Ophthalmology Times. July 11, 2025. Coverage of a presentation at Retina World Congress 2025. https://www.ophthalmologytimes.com/view/comparing-vorolanib-intravitreal-insert-with-aflibercept-in-dme-treatment

13. COMO. ClinicalTrials.gov identifier: NCT07449936. https://clinicaltrials.gov/study/NCT07449936

14. CAPRI. ClinicalTrials.gov identifier: NCT07449923. https://clinicaltrials.gov/study/NCT07449923