Retina Society 2026: LUGANO misses visual noninferiority endpoint for vorolanib insert in nAMD despite comparable anatomic control

The phase 3 LUGANO trial of vorolanib intravitreal insert (EYP-1901; Duravyu; EyePoint) did not meet its primary visual noninferiority endpoint vs aflibercept (Eylea; Regeneron) in neovascular age-related macular degeneration (nAMD). Anatomic outcomes were comparable between arms. Carl Regillo, MD, presented the primary efficacy results from the podium for the first time at the Retina Society 59th Annual Scientific Meeting in Los Angeles, California, and discussed them with Modern Retina.

Trial design

LUGANO and its identical companion trial, LUCIA, are prospective noninferiority trials. Each compares the tyrosine kinase inhibitor insert, dosed every 6 months, with on-label aflibercept 2 mg every 8 weeks over 2 years. Both arms received 3 monthly aflibercept loading doses before 1:1 randomization. Patients in either arm could receive supplemental aflibercept if they lost more than 5 letters and had a central subfield thickness (CST) increase of 75 µm or more vs their best on-study measurement.

The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 52 and 56, with a 4.5-letter noninferiority margin. LUGANO enrolled both treatment-naive and previously treated patients; approximately 75% were treatment naive. Mean baseline BCVA was approximately 20/50, and mean CST was approximately 320 µm. Fewer than 6% of patients discontinued, and there were no discontinuations due to adverse events with the vorolanib insert.

Primary outcome

At the primary endpoint, mean BCVA change was approximately +2 letters with the vorolanib insert vs close to +6 letters with aflibercept. CST reductions held through the maintenance phase, and the two arms finished within a few micrometers of each other. Regillo described the pairing of good exudative control with weaker visual results as “unexpected and unusual.”

Explaining the vision gap

More patients in the vorolanib arm lost 3 or more lines, and most of those cases had causes other than nAMD. Of 9 such patients, 6 progressed to foveal geographic atrophy (GA), 2 had glaucoma progression to a severe degree, and 1 had a retinal detachment with a poor visual outcome.

The aflibercept arm also outperformed expectations. One patient (0.5%) lost 3 or more lines. Regillo noted that rates of roughly 3% to 6% are typical with every-8-week aflibercept in phase 3 nAMD trials.

In a post hoc analysis excluding the 9 patients, the between-arm difference narrowed to 2.4 letters, which Regillo said would have met noninferiority. Median BCVA change, which limits the influence of outliers, showed a difference of about 1.4 letters.

Geographic atrophy analyses

Regillo reported no trend toward GA worsening with the vorolanib insert. GA rates were comparable between arms at baseline and at the primary endpoint. GA growth rates in the vorolanib arm did not differ from fellow eyes or natural history controls. At baseline, however, GA was located closer to the foveal center in the vorolanib arm.

Looking ahead

Regillo said most patients receiving the insert did not need supplemental injections. Results from LUCIA, he said, are expected within the next few months and will give a fuller picture of the therapy’s efficacy and safety.

REFERENCE

Regillo C. LUGANO phase 3 trial of bioerodible EYP-1901 (vorolanib intravitreal insert) vs aflibercept in patients with neovascular age-related macular degeneration (nAMD): first-time vision and anatomic outcomes. Presented at: The Retina Society 59th Annual Scientific Meeting; September 23-26, 2026; Los Angeles, CA. Session AMD I.