Duravyu misses primary end point in first pivotal wet AMD trial; secondary durability signals hold

Vorolanib intravitreal insert 2.7 mg (Duravyu) failed to meet the prespecified primary efficacy end point of the phase 3 LUGANO trial in neovascular (wet) age-related macular degeneration (AMD), EyePoint, Inc. reported in topline results released August 17, 2026.¹ Non-inferiority to aflibercept was reached only in an ad hoc analysis that excluded a small subgroup of patients, leaving the headline efficacy question to be settled by the second identical pivotal trial, LUCIA, expected in the fourth quarter of 2026.¹

“We are pleased to see that Duravyu provided clinically meaningful results in the LUGANO trial. The outstanding outcomes across key secondary endpoints, paired with visual improvement, reinforce our confidence in Duravyu’s potential to transform the current wet AMD treatment paradigm,” said Jay S. Duker, MD, President and CEO of EyePoint, in a news release.¹ “While the primary end point result for the full dataset was unexpected, the consistently positive results from the pre-specified secondary endpoints and the ad hoc analysis on the primary endpoint present a compelling case for Duravyu as a new potential therapeutic option for wet AMD. We look forward to a potential New Drug Application (NDA) filing with FDA in the first half of 2027, pending LUCIA results in the fourth quarter of 2026.”

LUGANO (NCT06668064) is a randomized, double-masked, aflibercept-controlled non-inferiority study, 1 of 2 identically designed phase 3 trials that together enrolled more than 900 patients with treatment-naïve or previously treated wet AMD.^1,2 Participants were randomized 1:1 to vorolanib intravitreal insert 2.7 mg administered every 6 months or to on-label aflibercept, with the primary end point defined as the average change in best-corrected visual acuity (BCVA) at weeks 52 and 56 relative to baseline.^1,2

According to the company, the primary end point was not achieved in the full analysis dataset. In an ad hoc analysis that removed 9 of 211 patients—described as an "asymmetric cohort"—who lost vision for reasons the company attributed to causes unrelated to wet AMD, vorolanib intravitreal insert 2.7 mg met non-inferiority to aflibercept with a nominal P value of .0096.¹

“The LUGANO results are clinically meaningful because the trial compared Duravyu to on-label aflibercept, the current gold standard control group in wet AMD trials. Nearly 80% of Duravyu-treated patients received one or no supplemental injections through Week 56. Disease control with this degree of durability, coupled with a favorable safety profile, would meaningfully reduce the treatment burden for our patients,” said Carl D. Regillo, MD, FACS, former director of the Wills Eye Hospital Retina Service, Professor of Ophthalmology, Thomas Jefferson University, in the release. “Duravyu's ability to control disease well in the majority of patients with a 6-month redosing interval represents a significant advance for our patients with wet AMD. In clinical practice, keeping patients adequately treated over time is a big challenge, and a sustained delivery option with this kind of profile would be a welcome addition to the armamentarium.”

EyePoint characterized the secondary end points as supportive: a reported 42% reduction in treatment burden versus on-label aflibercept (nominal P < .0001), roughly 2 fewer injections through week 56, and supplement-free rates of 76% through week 32 and 54% through week 56.¹ Anatomic measures showed a mean difference of 4 microns in central subfield thickness versus aflibercept at week 56.¹ The insert was described as safe and well tolerated on repeat dosing, with no observed migration, anterior chamber opacities, free-floating particles, vasculitis, or severe intraocular inflammation, and no differences from control in cataract, elevated intraocular pressure, or inflammation.¹

These findings warrant cautious interpretation. A missed primary end point on the prespecified, randomized analysis set is the central result; post hoc exclusion of patients, however clinically rationalized, generates hypotheses rather than confirmatory evidence, and the reported P values are nominal and unadjusted for multiplicity. Durability and treatment-burden benefits are consistent with the drug's earlier-phase profile but do not substitute for a met visual-acuity endpoint in a non-inferiority design, where the comparator itself is an active, effective therapy.

The clinical rationale for durable therapy remains substantial. Wet AMD is a leading cause of irreversible vision loss in adults older than 50 years, and the global burden of AMD is projected to reach roughly 288 million people by 2040.³ Standard of care relies on repeated intravitreal anti-VEGF injections, often every one to two months under treat-and-extend protocols; real-world cohorts consistently receive fewer injections than pivotal trials prescribed, a gap linked to undertreatment and vision decline over time.⁴ Longer-acting options—including higher-dose aflibercept 8 mg, now approved with dosing intervals up to 5 months—reflect the field's continued push to reduce injection frequency without sacrificing anatomic and functional control.⁵

“Duravyu demonstrated durable efficacy results with stable retinal anatomy maintained through Week 56, avoiding the sawtooth pattern commonly seen with intermittent anti-VEGF therapy. In addition, the supplement-free anatomic and visual outcomes further validate the potency of Duravyu,” said Ramiro Ribeiro, MD, PhD, Chief Medical Officer of EyePoint, in the release. “These findings represent an important advancement for retinal disease treatment, demonstrating the potential for repeat dosing of a tyrosine kinase inhibitor (TKI), a capability unique to our clinical program, coupled with a favorable safety profile. We extend our sincere gratitude to the patients, caregivers, and investigators whose partnership and dedication made this study possible.”

Vorolanib intravitreal insert 2.7 mg pairs vorolanib, a selective tyrosine kinase inhibitor (TKI) with intracellular VEGF-receptor and PDGFR activity, with a bioerodible sustained-release insert engineered for 6-month delivery.¹ The candidate previously met its primary end point in the phase 2 DAVIO 2 trial (NCT05381948), where single-injection EYP-1901 provided vision outcomes comparable to aflibercept every 8 weeks in previously treated patients while markedly reducing supplemental injections.^6,7 Vorolanib is investigational and not approved by the US FDA for any indication.¹

Next steps hinge on LUCIA. Because both trials were designed to support a marketing application, a discordant or negative LUCIA readout could complicate the regulatory path. EyePoint has stated it anticipates topline LUCIA data in the fourth quarter of 2026 and, contingent on results, a potential new drug application for wet AMD in the first half of 2027.¹ Full week-52/56 datasets, peer-reviewed publication, and clarity on the pre-specified statistical hierarchy will be needed before the LUGANO secondary signals can be weighed against the missed primary end point.

References

1. EyePoint, Inc. EyePoint announces topline data from LUGANO, the first of two pivotal phase 3 clinical trials for DURAVYU 2.7mg in wet AMD. GlobeNewswire. August 17, 2026. Accessed August 17, 2026. https://www.globenewswire.com/news-release/2026/08/17/3345965/0/en/eyepoint-announces-topline-data-from-lugano-the-first-of-two-pivotal-phase-3-clinical-trials-for-duravyu-2-7mg-in-wet-amd.html

2. Study of vorolanib intravitreal insert (DURAVYU) in wet age-related macular degeneration (LUGANO). ClinicalTrials.gov identifier: NCT06668064. Accessed August 17, 2026. https://clinicaltrials.gov/study/NCT06668064

3. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e116. doi:10.1016/S2214-109X(13)70145-1. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(13)70145-1/fulltext

4. Real-world treatment patterns in a population with neovascular AMD treated with anti-VEGF agents. PubMed record 34039184. Accessed August 17, 2026. https://pubmed.ncbi.nlm.nih.gov/34039184/ (Full author and citation details to be confirmed against the source record.)

5. Regeneron Pharmaceuticals. EYLEA HD (aflibercept) approved by FDA as first and only injectable anti-VEGF with dosing intervals up to 5 months for wet AMD and DME. GlobeNewswire. April 2, 2026. Accessed August 17, 2026. https://www.globenewswire.com/news-release/2026/04/02/3267657/0/en/EYLEA-HD-aflibercept-Approved-by-FDA-as-First-and-Only-Injectable-Anti-VEGF-with-Dosing-Intervals-Up-to-5-Months-for-Wet-Age-related-Macular-Degeneration-wAMD-and-Diabetic-Macular.html

6. Vorolanib intravitreal insert (EYP-1901) in subjects with wet age-related macular degeneration (DAVIO 2). ClinicalTrials.gov identifier: NCT05381948. Accessed August 17, 2026. https://clinicaltrials.gov/study/NCT05381948

7. A review of the DAVIO 2 phase 2 trial results. Modern Retina. Accessed August 17, 2026. https://www.modernretina.com/view/a-review-of-the-davio-2-phase-2-trial-results