Duravyu (vorolanib intravitreal insert)

The ClinicalTrials.gov record (last updated 2026-09-03) lists 76 locations, all in the United States, which is consistent with the 2025 Form 10-K description of LUGANO as the United States trial and LUCIA as the United States and ex-United States trial; the first-participant announcement and a 2025 congress poster described both trials as global. The first participant was dosed in October 2024 (registry study start 2024-10-22), enrollment was completed on May 27, 2025, the registry reports actual primary completion on 2026-07-13, and topline results were announced on August 17, 2026. Estimated study completion (week 96) is 2027-08.

The topline presentations report the primary endpoint as a mixed model for repeated measures (MMRM) estimate of change from baseline blended across weeks 52 and 56, tested against a margin of -4.5 letters. Efficacy tables use 211 participants in the vorolanib insert arm and 216 in the aflibercept arm (427 of 432 randomized participants, 98.8%); the ocular adverse event table uses 211 and 221 participants (432 of 432). The definition of the efficacy population, the method for handling missing data, the confidence interval for the full-dataset treatment difference, and any multiplicity procedure for secondary endpoints were not reported. All p-values for the ad hoc analysis, the prespecified supplement-free subgroup analysis, and the treatment burden endpoint were labeled nominal. The September 2026 presentation added a median regression analysis and a randomization simulation labeled as new analyses. All results were labeled preliminary and pending final analysis.

Of 432 randomized participants, 211 in the vorolanib insert arm and 216 in the aflibercept arm were included in efficacy analyses, and 211 and 221 in the ocular adverse event table. Discontinuation through week 56 was 6% in each arm, and none was attributed to the vorolanib insert. Reading center assessments at week 56 included 193 and 197 participants for subretinal fibrosis and 168 per arm for fundus autofluorescence. A full CONSORT flow was not reported.

LUGANO did not meet its primary endpoint of non-inferiority (margin -4.5 letters) in mean BCVA change from baseline to weeks 52 and 56 in the full dataset; the numeric treatment difference and confidence interval for the full dataset were not reported in text. In the full dataset, the vorolanib insert arm showed a mean BCVA gain from baseline. Nine of 211 participants (4.3%) in the vorolanib insert arm and none of 216 in the aflibercept arm lost 15 or more letters from causes the company attributed to conditions other than wet AMD (geographic atrophy, 6; glaucoma, 2; retinal detachment, 1). In an ad hoc analysis excluding these 9 participants, least squares mean BCVA change was +3.5 letters with the vorolanib insert and +5.9 letters with aflibercept (difference -2.4 letters; nominal p=0.0096). In the September 2026 presentation, a median regression analysis of all participants with week 52 or week 56 BCVA gave a median difference of -1.4 letters, and random reassignment of the 16 participants with any loss of 15 or more letters gave modeled differences of -1.3 to -2.0 letters. The presentation chart shows 15-letter or greater loss in 7.5% of the vorolanib insert arm (4.5% attributed to non-wet AMD causes) and 0.5% of the aflibercept arm.

Mean injections after loading through week 56 were 3.1 with the vorolanib insert and 5.3 with aflibercept, a 42% reduction (nominal p<0.0001), with an average of 1.1 supplemental injections annualized in the vorolanib insert arm. Supplement-free rates in the vorolanib insert arm were 76% through week 32 and 54% through week 56. In the supplement-free subgroup (113 participants receiving the vorolanib insert, compared with 192 aflibercept participants shown in the chart legend), BCVA change was +4.7 versus +6.4 letters (difference -1.8; nominal p=0.0035). Mean central subfield thickness change at week 56 was -72 µm versus -76 µm (difference +4 µm).

Through week 56, the vorolanib insert arm (211 participants) and aflibercept arm (221 participants) had cataract in 4.3% and 5.4%, increased intraocular pressure in 3.8% and 3.2%, intraocular inflammation in 0.5% and 0.5%, and retinal detachment in 0.5% and 0.5% of participants. Ocular adverse events reported more often with the vorolanib insert included conjunctival hemorrhage (11.4% versus 5.0%), vitreous floaters (9.0% versus 3.6%), neovascular AMD (7.1% versus 1.4%), retinal hemorrhage (4.7% versus 1.8%), retinal edema (2.8% versus 0.9%), and visual impairment (2.4% versus 0.0%). No insert migration into the anterior chamber, anterior chamber opacities, free-floating particles, retinal vasculitis, or severe intraocular inflammation were reported. Serious adverse events, systemic adverse events, and endophthalmitis counts were not reported numerically; endophthalmitis was reported at less than 1% in both arms.

• The primary endpoint was not met in the full dataset. Non-inferiority was shown only in an ad hoc analysis that removed 9 of 211 participants (4.3%) in the vorolanib insert arm whose loss of 15 or more letters was attributed by retina specialists to causes other than wet AMD; the same attribution identified 0 of 216 aflibercept participants, and p-values for this and all secondary analyses are nominal.
• The full-dataset treatment difference and its confidence interval, the multiplicity procedure, missing data handling, and the efficacy population definition have not been reported; results are topline, labeled preliminary and pending final analysis, and were not peer reviewed as of September 2026.
• The aflibercept arm had a 0.5% rate of 15-letter or greater loss, lower than the 2.7% to 7.7% rates the sponsor cited from earlier trials, while the vorolanib insert arm had 7.5%. The sponsor attributes the imbalance to chance and to baseline differences; this cannot be confirmed from one trial, and the LUCIA results will be the direct test.
• Baseline imbalances favored the aflibercept arm on some risk factors for vision loss unrelated to neovascular activity: glaucoma history 11.4% versus 5.9%, total CNV area 5.69 versus 4.60 mm2, and geographic atrophy located closer to the fovea (825 versus 1009 µm); eligibility excluded only center-subfield atrophy.
• Vorolanib insert participants received three aflibercept loading doses before the first insert, supplemental aflibercept was available in both arms, and the supplement criteria wording differs between 2025 and 2026 company presentations; the efficacy therefore reflects a regimen of aflibercept loading plus insert plus supplemental aflibercept, not insert monotherapy.
• The comparator was fixed aflibercept 2 mg every 8 weeks, not treat-and-extend dosing, faricimab, or aflibercept 8 mg, and all 76 registry sites were in the United States.
• Efficacy is reported to week 56 only; year 2 is a safety-only continuation, no patient-reported outcome or quality-of-life data have been reported, and systemic and serious adverse event data are not yet public.
• Treatment burden was compared with a fixed aflibercept schedule that allows a maximum 60% reduction, so the 42% reduction measures scheduled injection frequency rather than burden relative to extended-interval regimens.