EyePoint’s DURAVYU misses first Phase 3 endpoint in wet AMD, putting focus on second trial

EyePoint Pharmaceuticals’ experimental sustained-release treatment DURAVYU has failed to meet the primary endpoint in the first of two pivotal Phase 3 trials in wet age-related macular degeneration (AMD), creating a setback for the company’s bid to offer a longer-acting alternative to established anti-VEGF treatments.

The LUGANO trial did not demonstrate non-inferiority to aflibercept, the active ingredient in Regeneron’s Eylea, in the full analysis set. However, EyePoint argues that an unusually high number of patients in the DURAVYU arm experienced significant vision loss unrelated to wet AMD, which it says confounded the primary analysis.

The company reported that nine of 211 patients receiving DURAVYU experienced vision loss of at least 15 letters unrelated to wet AMD. No patients in the aflibercept control arm experienced comparable vision loss.

An ad hoc analysis excluding those nine patients found DURAVYU to be non-inferior to aflibercept, with a nominal p-value of 0.0096. However, because the primary endpoint was not met in the full dataset, the result does not replace the prespecified analysis.

The development leaves the future of DURAVYU dependent to a significant degree on the second pivotal trial, LUCIA, with topline results expected in the fourth quarter of 2026.

Primary endpoint missed despite secondary results

LUGANO compared a 2.7mg dose of DURAVYU, an intravitreal insert containing the tyrosine kinase inhibitor vorolanib, with on-label aflibercept.

The primary endpoint assessed the average change from baseline in best-corrected visual acuity (BCVA) at Weeks 52 and 56.

While the full dataset failed to demonstrate non-inferiority, EyePoint highlighted a number of positive secondary outcomes, particularly around treatment durability.

DURAVYU reduced treatment burden by 42% compared with on-label aflibercept, which EyePoint says translated into an average of two fewer injections through Week 56. The treatment achieved statistical superiority on this endpoint, with a nominal p-value of less than 0.0001.

The company also reported that 54% of DURAVYU-treated patients remained supplement-free through Week 56, while 79% received either zero or one supplemental injection.

At Week 32, 76% of patients were supplement-free and 94% had received no more than one supplemental injection.

Among supplement-free patients, a prespecified analysis of BCVA showed DURAVYU was non-inferior to aflibercept, with a nominal p-value of 0.0035.

EyePoint also reported broadly comparable safety between the treatment and control groups, with no observed cases of insert migration, anterior chamber opacities, free-floating drug particles, retinal vasculitis or severe intraocular inflammation.

An unusual imbalance

The central issue surrounding the LUGANO result is the nine patients who experienced significant vision loss unrelated to wet AMD.

EyePoint argues that the finding was unusually concentrated in the DURAVYU arm. The company cites historical Phase 3 aflibercept trials in which approximately 3–5% of patients experienced vision loss of at least 15 letters for reasons unrelated to the disease.

In LUGANO, that pattern appeared in the DURAVYU arm but not the aflibercept group.

The company says the cases contributed to the failure of the primary endpoint and prompted an ad hoc analysis examining the results without those patients.

However, the cause of the vision loss remains an important question. EyePoint's current position is that the losses were not related to DURAVYU or inadequate control of wet AMD, but further analysis will be required to understand the cases and their implications.

Why the result matters

DURAVYU is being developed as a sustained-release alternative to frequent anti-VEGF injections for wet AMD, with the potential to provide treatment at six-month intervals.

That could address a significant challenge in wet AMD, where maintaining regular treatment over the long term can be difficult for patients and healthcare providers.

The LUGANO results therefore represent a mixed picture. The primary efficacy endpoint was missed, but the treatment demonstrated a substantial reduction in injection burden alongside positive anatomical and supplement-free outcomes.

That distinction is important because a reduction in treatment frequency alone is unlikely to be sufficient if visual outcomes cannot be shown to be comparable with current standards of care.

LUCIA becomes the key test

EyePoint now expects topline data from LUCIA in the fourth quarter of 2026.

The two trials were designed as identical Phase 3 studies, each comparing DURAVYU administered every six months with on-label aflibercept. More than 900 patients have been enrolled across the programme.

The company continues to anticipate a potential New Drug Application submission to the US Food and Drug Administration in the first half of 2027, subject to the LUCIA results.

The possibility of moving forward following one unsuccessful pivotal study and one successful study is not unprecedented, although the regulatory path would remain dependent on the totality of the evidence.

The market reaction has nevertheless highlighted the uncertainty surrounding the programme, with EyePoint's shares falling sharply following the announcement.

For now, DURAVYU's development programme remains active, but the focus has shifted firmly to LUCIA. A successful second Phase 3 readout could help determine whether the unusual LUGANO result was an isolated statistical imbalance or a more fundamental challenge to the drug's efficacy profile.

EyePoint is also developing DURAVYU for diabetic macular oedema, with Phase 3 trials COMO and CAPRI expected to report topline results in the fourth quarter of 2027.