EURETINA 2026: Duravyu misses LUGANO endpoint but cuts treatment burden by 42%
At EURETINA 2026, Roger Goldberg, MD, MBA, explains why EYP-1901 missed LUGANO's primary endpoint despite matched anatomy, clean safety and a 42% cut in treatment burden.
EyePoint's sustained-release tyrosine kinase inhibitor (TKI) EYP-1901 (Duravyu; vorolanib intravitreal insert) missed its primary endpoint in LUGANO, the first of 2 pivotal phase 3 trials in neovascular age-related macular degeneration (AMD), according to top-line data the company released in August 2026.1 The trial compared EYP-1901 2.7 mg dosed every 6 months with on-label aflibercept 2 mg every 8 weeks in 432 randomised patients.1
At EURETINA 2026 in Vienna, Austria, Roger Goldberg, MD, MBA, of Bay Area Retina Associates in Walnut Creek, California, presented the top-line findings. In this interview with Ophthalmology Times Europe, he explains the trial design, why a small group of patients losing vision from causes other than wet AMD may account for the result, and what the data show about anatomic control, geographic atrophy, safety and durability.
Editor's note: This transcript has been lightly edited for clarity.
What is EYP-1901, and how does its mechanism differ from current anti-VEGF agents?
Roger A. Goldberg, MD, MBA: EYP-1901 is a bioerodible implant that is injected into the vitreous cavity. It contains 94% vorolanib, which is a potent tyrosine kinase inhibitor, or TKI. TKIs work a little bit differently, inhibiting VEGF receptor signalling intracellularly, and vorolanib also inhibits the IL-6 receptor and the PDGF receptor. The matrix doesn't contain any PEG or PLGA, and it slowly releases vorolanib over a period of 6 months or longer with first-order kinetics.
How was LUGANO designed?
Goldberg: The LUGANO study was one of 2 paired phase 3 trials, and it enrolled both treatment-naive and previously treated patients with neovascular AMD. Patients were randomised 1:1 to receive EYP-1901 every 6 months after 3 aflibercept loading doses, versus a standard of aflibercept 2 mg every 8 weeks after the same 3 loading doses.
The primary endpoint was the mean change in best-corrected visual acuity (BCVA), averaged between weeks 52 and 56, with a standard noninferiority margin of 4.5 letters. Patients in both arms could be rescued, or receive supplemental aflibercept injections, if they had either a vision-threatening macular haemorrhage or lost 5 letters of visual acuity coupled with a 75-micron increase in central subfield thickness (CST).
What did the patient population look like at baseline?
Goldberg: The baseline characteristics were well balanced across both arms. Seventy-five per cent of patients were treatment naive, average CST was 320 microns, and average visual acuity was about 20/50.
What were the top-line visual acuity results?
Goldberg: The trial actually missed the noninferiority margin, with a difference of 3.8 letters of visual acuity gain between the aflibercept control arm and the EYP-1901 arm. This happened despite excellent anatomic control, with a CST curve in the EYP-1901 arm very much akin to that of the aflibercept 2 mg arm. At week 56, there was only a 4-micron difference in CST.1
What explains the disconnect between anatomic control and visual acuity?
Goldberg: We did a post hoc analysis looking at all the patients who lost 15 or more letters of visual acuity in 1 year. What were the drivers of that? It turns out that there were 9 patients who lost visual acuity due to causes other than wet macular degeneration, and all 9 of those patients were in the EYP-1901 arm. This asymmetric cohort consisted of 6 patients who lost vision due to geographic atrophy, 2 from glaucoma and 1 from a retinal detachment. If you exclude those 9 patients, the rest of the cohort was actually noninferior in visual acuity.1
The aflibercept control arm also performed better than average. In historic registration trials in wet macular degeneration, typically 3% to 6% of patients will lose 15 letters or more.2 In LUGANO, only 1 patient, 0.5% of the aflibercept control arm, lost 15 or more letters of vision.
Was the top-line result a surprise, given the rescue criteria?
Goldberg: Yes, the top-line result was surprising, because patients could be rescued if they lost 5 letters of vision. Because of that, you would expect them to stay within the noninferiority margin of 4.5 letters. That's why it's interesting that these 9 patients lost vision due to causes other than wet macular degeneration. Six of those 9 patients actually did receive supplemental injections, which didn't help improve their vision at all, because the reason they were losing vision wasn't wet macular degeneration.
Given that 6 of those patients developed geographic atrophy, could EYP-1901 cause or accelerate it?
Goldberg: We actually looked at this in a number of different ways, and we don't see that. For new-onset geographic atrophy, there was no difference between the EYP-1901 and aflibercept arms. When we look at the growth of geographic atrophy, there was no difference in EYP-1901-treated eyes versus fellow-eye controls, with a growth rate of 1.6 to 1.7 mm² in that first year, which is actually less than the typical published average. And when we look at growth rate in terms of proximity to the foveal centre, we see no difference between the EYP-1901 arm and the aflibercept control arm. So it doesn't seem to be inducing geographic atrophy.
How did EYP-1901 perform on safety?
Goldberg: The safety of EYP-1901 looked excellent. There were no cases of free-floating particles, anterior chamber opacities, anterior chamber migration, occlusive or nonocclusive vasculitis, or severe intraocular inflammation.1
And on durability, the main rationale for the implant?
Goldberg: Why are we developing this drug at all? It's really about durability, and we saw excellent results, actually superiority, in terms of number of injections, with a 42% reduction in treatment burden after those first 3 loading doses. Eighty percent of patients in the EYP-1901 arm were able to go the whole year with either 0 or 1 supplemental injection.1
How would you summarise LUGANO, and what are you watching for next?
Goldberg: The trial missed on the primary endpoint, but that seems to be driven by this asymmetric cohort. We saw excellent anatomic control, a favourable safety profile and great durability. In a couple of weeks, we should get the LUCIA results, which is the twin phase 3 study, and that will help further inform our understanding of this molecule.
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References
EyePoint announces topline data from LUGANO, the first of two pivotal phase 3 clinical trials for DURAVYU 2.7mg in wet AMD. News release. EyePoint, Inc. August 17, 2026. Accessed October 2, 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 Heier JS, Brown DM, Chong V, et al; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. doi:10.1016/j.ophtha.2012.09.006
