40% Fewer Injections but Efficacy Threshold Still Missed: DURAVYU Phase 3 Wet AMD Trial Fails

For patients with wet age-related macular degeneration, maintaining vision often means receiving repeated intravitreal injections for years. EyePoint hopes to ease this burden with DURAVYU, a sustained-release therapy administered once every six months, but the first pivotal Phase 3 trial, LUGANO, delivered mixed results: the number of injections did decline, but the most important visual acuity efficacy threshold was not met.

LUGANO is a randomized, double-masked, parallel-group trial comparing 2.7 mg DURAVYU with the standard 2 mg dose of aflibercept. DURAVYU places the tyrosine kinase inhibitor vorolanib in a biodegradable sustained-release intravitreal delivery system, with the goal of dosing once every six months; the control group received aflibercept according to its approved regimen. Trial registration data show that the study was expected to enroll approximately 400 patients aged 50 years or older, with the primary endpoint being the average change from baseline in best-corrected visual acuity at weeks 52 and 56.

In the full dataset, DURAVYU failed to demonstrate that its visual acuity performance was noninferior to aflibercept, meaning the trial formally missed its primary endpoint. EyePoint said that nine of the 211 DURAVYU participants experienced a decline of at least 15 letters in visual acuity, with the causes determined to be unrelated to wet age-related macular degeneration; there were no comparable cases in the aflibercept group. However, this classification of causes currently comes primarily from the company’s topline data release, while the full data, the magnitude of visual acuity changes in each group, and the basis for the individual case determinations have not yet been disclosed.

After excluding these nine patients, DURAVYU achieved noninferiority in a post hoc analysis, with a nominal P value of 0.0096. This result suggests that a small number of outlier cases may have substantially affected the overall interpretation, but it cannot replace the prespecified primary analysis; excluding patients post hoc may also introduce bias. A second Phase 3 trial with the same design, LUCIA, will therefore become key evidence in determining whether this was a chance imbalance or a reproducible efficacy gap.

On the other hand, DURAVYU showed a clear signal in reducing treatment burden. By week 56, patients required 42% fewer treatments, equivalent to an average of two fewer injections; 54% of patients required no supplemental aflibercept, while 79% received either zero or one supplemental injection. The company also said there were no differences between the two groups in cataracts, increased intraocular pressure, or intraocular inflammation, but rarer or later-emerging risks will require the full safety data and two years of follow-up.

These results highlight the dilemma facing long-acting ophthalmic therapies: reducing clinic visits and injections has clinical value, but only if vision is reliably maintained. EyePoint expects to announce topline LUCIA results in the fourth quarter of 2026 and had planned to submit a U.S. new drug application in the first half of 2027 depending on those results. With the first trial now having missed its primary endpoint, the subsequent regulatory path will depend not only on the magnitude of the reduction in injections, but also on whether the second trial can deliver consistent and complete evidence of visual acuity efficacy without relying on post hoc exclusions.