In this interview, Tarek S. Hassan, Chief Strategic Science Officer for EyePoint, discusses topline results from the randomized, double-masked Phase 3 LUGANO trial evaluating DURAVYU (EYP-1901) 2.7 mg versus on-label aflibercept 2 mg every 8 weeks (q8W) in wet AMD.

DURAVYU is a bioerodible intravitreal insert providing sustained release of vorolanib for at least six months. Vorolanib is a tyrosine kinase inhibitor (TKI) whose primary pharmacology in wet AMD is intracellular inhibition of VEGF receptor signaling; it also inhibits the PDGF receptor, with effects on IL-6 signaling demonstrated in nonclinical studies (1). LUGANO did not demonstrate non-inferiority for the primary endpoint of mean change in best-corrected visual acuity (BCVA) in the full dataset. Importantly, mean vision nevertheless improved in the full DURAVYU cohort. The result was materially affected by an unexpected imbalance of nine DURAVYU-treated patients with ≥15-letter vision loss not attributable to inadequate control of neovascular AMD. Key secondary endpoints demonstrated strong anatomic control, durability, reduced treatment burden, and a favorable safety profile, supporting confidence as LUCIA approaches.

Why are you confident that the asymmetry is driving the miss? Can you tell us more about these nine cases? Did DURAVYU cause any adverse events that led to more vision loss?

The prespecified primary endpoint was not met in the full analysis set, and we have to start there. As a retina specialist, the next question is why. Nine of 211 DURAVYU-treated patients had ≥15-letter vision loss from causes not attributable to failure to control neovascular AMD. Six had good anatomic control but lost vision in association with geographic atrophy, two had severe glaucoma, and one had a retinal detachment followed by cataract. Six received supplemental aflibercept, but none recovered vision. Clinically, that provides additional evidence that inadequate VEGF suppression was not the explanation.

These nine patients accounted for 258 letters of vision loss. Even including them, mean VA improved in the full DURAVYU arm. The other 202 patients gained 3.5 letters on average. In the ad hoc analysis excluding the nine eyes, the difference versus aflibercept fell within the prespecified non-inferiority margin and achieved statistical non-inferiority. That does not change the prespecified full-dataset result, but it is important to understand what drove it. Only 0.5% of patients in the LUGANO aflibercept arm experienced ≥15-letter vision loss, considerably lower than rates reported in other pivotal Phase 3 studies (2-5). Cross-trial comparisons require caution, but this reinforces how unusual the distribution was. Repeated randomization simulations also supported the impact of this imbalance on the primary endpoint.

Repeat dosing of DURAVYU was well tolerated, with no meaningful imbalance in cataract, elevated intraocular pressure, intraocular inflammation, dry AMD, or retinal detachment. We did not identify a safety signal that explains the vision-loss imbalance.

Did you see the same asymmetry in the Phase 2 DAVIO 2 trial?

No, we did not see the same pattern in DAVIO 2. At Week 56, ≥15-letter loss occurred in 4.3% of DURAVYU patients versus 7.7% of aflibercept controls. No DURAVYU patients had ≥15-letter loss due to glaucoma or macular atrophy; one aflibercept patient lost vision due to geographic atrophy. DAVIO 2 does not suggest a consistent drug-related risk. LUCIA will provide another independent Phase 3 dataset.

What did the key secondary endpoints reveal regarding durability and supplementation?

The durability results are among the most encouraging findings from LUGANO. At Week 32, 76% of DURAVYU-treated patients remained supplement-free and 94% required zero or only one supplemental aflibercept injection. By Week 56, 54% remained supplement-free and 79% required zero or only one supplement. DURAVYU reduced treatment burden by 42% versus on-label aflibercept q8W, or approximately two fewer injections through Week 56. Because 60% was the maximum possible reduction under the trial design, 42% represents a substantial reduction against an actively treated standard-of-care control.

Anatomic disease control was also strong. The CST difference versus aflibercept q8W was only 4 µm through Week 56; among the 54% requiring no supplemental aflibercept, it was only 3 µm. To me, that is compelling evidence of durable biologic control in a substantial proportion of patients.

What is the plan with the FDA to gain approval?

The next major piece of evidence is LUCIA. LUGANO generated a clinically informative Phase 3 dataset, and LUCIA will allow us – and ultimately the FDA – to evaluate the program in its totality. LUCIA is expected to report topline results in Q4 2026. We are targeting an NDA submission in the first half of 2027, with the ultimate regulatory path determined with the FDA based on the totality of evidence across both studies.

If approved, what do these data tell you about DURAVYU’s place in the market?

Anti-VEGF therapy works extremely well in wet AMD. The challenge is delivering treatment consistently over many years. That is where DURAVYU could be important: sustained intracellular VEGF receptor inhibition with planned six-month dosing, with supplementation when needed.

LUGANO showed strong anatomic disease control with substantially fewer injections than on-label q8W aflibercept. If that efficacy, durability, and favorable safety profile are confirmed across the Phase 3 program, with LUCIA as the next critical readout, DURAVYU could address a major unmet need in wet AMD – keeping patients continuously treated and well controlled with far fewer injections.

Tarek S. Hassan, MD, is Senior Vice President, Chief Strategic Science Officer at EyePoint. Additionally, Dr. Hassan is currently Professor of Ophthalmology at Oakland University William Beaumont School of Medicine and a Senior Partner at Associated Retinal Consultants in Royal Oak, Michigan. Financial disclosures: Employee - EyePoint