EyePoint, Inc. has reported mixed results from the pivotal Phase 3 LUGANO trial of DURAVYU in wet age-related macular degeneration, with the sustained-delivery treatment failing to meet its primary endpoint in the full study population despite substantially reducing the need for supplemental eye injections. The trial compared DURAVYU 2.7 milligrams administered every six months with on-label aflibercept and was designed to demonstrate non-inferiority in best corrected visual acuity. EyePoint, Inc. attributed the miss partly to nine of 211 DURAVYU-treated patients who experienced losses of at least 15 letters that the company characterized as unrelated to wet AMD, while no corresponding cases occurred in the aflibercept control arm. An ad hoc analysis excluding those nine patients achieved non-inferiority with a nominal p-value of 0.0096, but the prespecified primary analysis of the full dataset remains negative.
The result places considerably greater importance on LUCIA, EyePoint, Inc.’s second identically designed pivotal Phase 3 wet AMD trial, which is expected to report topline data during the fourth quarter of 2026. Management continues to contemplate a New Drug Application during the first half of 2027 if the overall Phase 3 package supports filing, but the path has become less straightforward because regulators will have to evaluate a failed primary endpoint alongside positive secondary outcomes and the forthcoming independent LUCIA result.
Nine unexpected vision-loss cases complicate interpretation of the failed LUGANO primary endpoint
LUGANO and LUCIA are randomized, double-masked Phase 3 trials that together enrolled more than 900 patients with active wet age-related macular degeneration, including both treatment-naive and previously treated patients. Participants were randomized equally to receive DURAVYU every six months or on-label aflibercept, with average change from baseline in best corrected visual acuity at weeks 52 and 56 serving as the primary endpoint.
The full LUGANO dataset did not demonstrate the required non-inferiority. EyePoint, Inc. said the outcome was affected by nine DURAVYU patients, representing approximately 4% of that treatment group, who lost at least 15 letters for reasons the company determined were unrelated to wet AMD or inadequate control of the disease. No patients in the aflibercept arm experienced a comparable unrelated vision loss, creating an imbalance that EyePoint, Inc. believes disproportionately affected the mean visual-acuity comparison.
Removing those nine patients in a post-hoc analysis changed the result, with DURAVYU meeting the non-inferiority criterion against aflibercept at a nominal p-value of 0.0096. That analysis provides a potential explanation for the primary-endpoint failure, but it carries less evidentiary weight than the prospectively specified full-population analysis because the exclusion was made after examining the data. Regulators will therefore need to determine whether the nine cases represent a credible external source of noise or whether the full randomized result more accurately reflects the treatment’s performance.
The second pivotal trial could provide an unusually important test of that explanation. Because LUCIA uses essentially the same design, dosing strategy and endpoint, a clean non-inferiority result would strengthen the argument that the LUGANO miss resulted from an atypical imbalance rather than inadequate efficacy. Another miss would make reliance on the ad hoc analysis substantially more difficult and could materially alter EyePoint, Inc.’s planned regulatory strategy.
DURAVYU reduced treatment burden by 42% while maintaining strong anatomical disease control
The negative primary endpoint contrasts with several favorable secondary outcomes. DURAVYU reduced treatment burden by 42% compared with on-label aflibercept, achieving superiority with a nominal p-value below 0.0001 and translating into approximately two fewer injections per patient through week 56. EyePoint, Inc. designed DURAVYU around six-month redosing, seeking to address one of the central limitations of current wet AMD management, which often requires repeated intravitreal anti-VEGF injections over many years.
Supplement-free rates also supported the durability argument. Approximately 76% of DURAVYU-treated patients required no supplemental aflibercept through week 32, while 94% received either zero or one supplemental injection. At week 56, 54% remained entirely supplement free and 79% had required no more than one additional injection. A prespecified analysis among supplement-free DURAVYU patients demonstrated non-inferiority in visual acuity compared with supplement-free aflibercept patients, with a nominal p-value of 0.0035.
Anatomical control was similarly close between treatment groups. Central subfield thickness differed by an average of four microns between DURAVYU and aflibercept at week 56, while DURAVYU patients who remained supplement free showed only a three-micron difference. These optical coherence tomography findings suggest sustained suppression of retinal fluid and disease activity even when supplemental injections were avoided for substantial periods.
Safety did not reveal an obvious problem that would independently undermine development. EyePoint, Inc. reported no meaningful difference between DURAVYU and control in cataracts, elevated intraocular pressure or intraocular inflammation, while there were no observed cases of insert migration, retinal vasculitis, severe intraocular inflammation or free-floating drug particles. The combination of reduced injection frequency and acceptable repeat-dose safety therefore remains clinically attractive despite the failure of the main visual-acuity endpoint.
LUCIA has become the decisive test for whether DURAVYU can still support a 2027 FDA filing
DURAVYU combines vorolanib, a tyrosine kinase inhibitor, with EyePoint, Inc.’s bioerodible sustained-delivery technology. The treatment is designed to release drug for at least six months and inhibit VEGF receptors and PDGFR intracellularly, while EyePoint, Inc. has also reported preclinical evidence of activity involving IL-6 and JAK1 signaling. The product is delivered through a standard intravitreal injection in a physician’s office, allowing it to fit into existing retinal treatment infrastructure without an implanted permanent device.
The value proposition is built primarily around durability. Wet age-related macular degeneration requires ongoing treatment to prevent progressive vision loss, and frequent injections can create adherence and capacity challenges for patients, caregivers and retinal practices. A therapy capable of maintaining disease control with six-month redosing could materially reduce that burden if visual outcomes remain competitive with established anti-VEGF treatment.
That commercial proposition remains intact after LUGANO, but the regulatory evidence has become substantially less certain. EyePoint, Inc. said it still anticipates the possibility of filing an NDA in the first half of 2027, pending LUCIA results in the fourth quarter. Additional LUGANO subgroup analyses are expected to be presented at retina conferences beginning with the Retina Society Annual Scientific Meeting in September.
EyePoint, Inc. also has two fully enrolled Phase 3 trials evaluating DURAVYU in diabetic macular edema. COMO and CAPRI enrolled more than 480 patients in approximately five months, with topline results expected during the fourth quarter of 2027. That broader program means the implications of LUGANO extend beyond one indication, although the diabetic macular edema trials represent separate clinical tests and cannot be assumed to reproduce the wet AMD outcome.
EyePoint shares collapse as investors sharply reduce expectations for DURAVYU approval
The market response has been severe. EyePoint, Inc. shares were trading around $4.60 during the August 17 session, down approximately 68.8% from the previous close of $14.75, after trading as low as $3.52. More than 38 million shares had changed hands, and the company’s market capitalization had fallen to approximately $399 million.
The selloff indicates that investors are assigning substantially greater regulatory risk to DURAVYU following the failed primary endpoint, even though multiple secondary measures favored the treatment. The distinction between a prespecified endpoint failure and a favorable ad hoc analysis is particularly important in pivotal development because regulatory decisions generally place greater weight on prospectively defined analyses. LUCIA has therefore shifted from being a second confirmatory readout to potentially becoming the central evidence determining whether the wet AMD program can recover its original filing trajectory.
EyePoint, Inc. had approximately $180 million in cash, cash equivalents and marketable securities at June 30 and previously expected those resources to fund operations into the fourth quarter of 2027. Second-quarter operating expenses were $97.9 million as the company funded four Phase 3 trials and expanded its commercial manufacturing capabilities, while the quarterly net loss reached $94.5 million.
The balance sheet gives EyePoint, Inc. time to obtain the LUCIA result and continue the diabetic macular edema program, but the LUGANO miss substantially increases the importance of capital discipline. A positive LUCIA readout could restore confidence that DURAVYU offers competitive vision preservation with meaningfully fewer injections, while another primary-endpoint failure would raise much larger questions around the wet AMD filing and the value attributed to the sustained-delivery platform.
LUGANO therefore produced a result that is neither a straightforward clinical failure nor the pivotal success EyePoint, Inc. needed. DURAVYU clearly demonstrated substantial treatment-burden reduction, strong anatomical control and encouraging supplement-free durability, but it did not meet the trial’s prespecified primary endpoint in the population regulators were intended to evaluate. The fourth-quarter LUCIA readout will now determine whether those secondary strengths can remain part of a credible FDA approval strategy or whether the first Phase 3 miss represents a more fundamental problem for the wet AMD program.
