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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.

The ClinicalTrials.gov record (last updated 2026-09-03) lists 113 locations: 78 in the United States, 7 in Israel, 7 in Poland, 6 in India, 5 in Brazil, 4 in Hungary, 3 in Czechia, and 1 each in Germany, Slovakia, and the United Kingdom. The 2025 enrollment completion announcement also names participation in Australia, which the registry does not list. The first participant was dosed in December 2024 (registry study start 2024-11-27), enrollment was completed on July 29, 2025, primary completion is estimated for 2026-10, topline data are expected in the fourth quarter of 2026, and study completion is estimated for 2027-10.

LUCIA uses the same primary endpoint and -4.5-letter margin as LUGANO. The sponsor cites non-inferiority margin precedent from recent FDA approvals in neovascular AMD, and published phase 3 trials in neovascular AMD used margins of 4.5 letters (Archway, port delivery system with ranibizumab) or 4 letters (TENAYA and LUCERNE, faricimab; PULSAR, aflibercept 8 mg).

• No LUCIA efficacy or safety results have been reported as of September 2026; topline data are expected in the fourth quarter of 2026, and the only safety information is interim masked data pooled with LUGANO.
• The sponsor states that learnings from LUGANO were included in the LUCIA analysis plan before LUCIA topline results; the content of these changes has not been disclosed, and changes made after results of an identical trial are known may affect how the LUCIA primary analysis is interpreted.
• The design is identical to LUGANO, so the same design limitations apply: three aflibercept loading doses before the first insert, supplemental aflibercept in both arms, a fixed aflibercept 2 mg every 8 weeks comparator, a -4.5-letter margin, efficacy assessed to week 56 with safety-only follow-up in year 2, and exclusion of only center-subfield atrophy.
• Enrollment (475 participants) exceeded the registry estimate of 400, and the registry lists 113 sites in 10 countries, 78 (69.0%) of them in the United States; the registry does not list Australia, which the sponsor named as a participating country.
• If LUCIA meets its primary endpoint, the planned New Drug Application would rest on one trial meeting and one identical trial not meeting the prespecified primary endpoint, together with pooled data.

DAVIO 2 randomized 161 participants; the full analysis set included 156 (54 aflibercept 2 mg every 8 weeks, 50 EYP-1901 2060 mcg, 52 EYP-1901 3090 mcg). For the primary endpoint (BCVA change averaged over weeks 28 and 32), the registry reports least-squares mean changes of 1.17, 1.05, and 0.87 letters, with differences versus aflibercept of -0.12 letters (95% CI, -2.48 to 2.24) for 2060 mcg and -0.31 letters (95% CI, -2.63 to 2.02) for 3090 mcg; both lower confidence limits were above the -4.5-letter noninferiority margin. EyePoint's topline release reported differences of -0.3 and -0.4 letters. At week 56, mean BCVA change was 1.1 letters with aflibercept, 0.3 letters with 2060 mcg, and -1.9 letters with 3090 mcg. Up to week 32, 62.5% and 63.5% of EYP-1901 participants received no supplemental aflibercept, compared with 94.3% of aflibercept participants; at week 56, the proportions were 42.6%, 46.2%, and 82.7%. The normalized number of aflibercept injections through week 56 was 3.45 and 3.36 in the EYP-1901 arms and 6.33 in the aflibercept arm.

DAVIO 2 was a phase 2 trial with 50 to 54 participants per arm in the full analysis set, conducted at 39 sites in the United States, with 154 of 156 participants (98.7%) reported as White. Eligibility required a documented anatomic response to prior anti-VEGF therapy, at least 2 anti-VEGF injections in the prior 6 months, and CST of 350 µm or less, so treatment-naive eyes and eyes with greater baseline exudation were not studied. All arms received aflibercept loading at day 1, week 4, and week 8, including an aflibercept injection given with the EYP-1901 insert at week 8. The tested doses (2060 mcg and 3090 mcg, single administration) differ from the 2.7-mg dose given every 6 months in phase 3. The primary endpoint was measured 20 to 24 weeks after insert administration; the week 56 BCVA, supplement-free, and injection-count outcomes are descriptive secondary outcomes without reported hypothesis tests. Company presentations defined the full analysis set as participants who received both day 1 and week 8 treatments, whereas the registry describes it as participants who received at least 1 dose, and company-reported differences for the primary endpoint (-0.3 and -0.4 letters) differ from the registry least-squares differences (-0.12 and -0.31 letters). Several subgroup and time-in-range analyses were post hoc. No peer-reviewed full publication of DAVIO 2 was identified; most results come from sponsor press releases, sponsor-funded congress presentations, and the registry record.

In DAVIO, 17 participants with previously treated wet age-related macular degeneration received a single EYP-1901 injection at 440 to 3090 μg, and 16 were included in efficacy analyses. Mean BCVA change from baseline was -1.8 letters at 6 months and -5.4 letters at 12 months, and mean CST change was +1.7 μm and +2.4 μm. At 12 months, 6 of 16 participants (37.5%) had lost 5 or more letters. Treatment burden, compared with a normalized pre-enrollment count, was reduced by 74% at 6 months and 71% at 12 months. Of 16 study eyes, 13 (81%), 8 (50%), and 5 (31%) required no additional anti-VEGF injection up to 3, 6, and 12 months, respectively. The study had no control arm, was open label, and was not powered for efficacy.

DAVIO enrolled 17 participants across 4 dose cohorts (1 to 8 participants per cohort) at 11 sites in the United States, without a control arm or masking, and no formal sample size calculation was performed. Four participants in the planned 3090-μg cohort received fewer inserts than planned because of injector difficulties and were reassigned to lower-dose cohorts. Efficacy and treatment-burden analyses were descriptive, excluded 1 participant who withdrew after week 16, and were added post hoc, with pre-enrollment treatment burden normalized from historical records. The authors state that unmasked investigators may have been biased in deciding on supplemental injections. The eligibility criteria (3 or more prior injections of the same agent in 6 months, dosing 7 to 10 days after the last anti-VEGF injection) limit applicability to treatment-naive participants, and the doses tested differ from the 2.7-mg phase 3 dose. The publication was sponsored by EyePoint, and 2 authors were EyePoint employees.

APEX evaluated daily oral vorolanib (X-82) at 50, 100, and 200 mg, not the intravitreal insert, so its efficacy results do not transfer directly to EYP-1901; its relevance to this report is the systemic adverse event profile of vorolanib at oral exposures. The trial randomized 157 participants and was stopped early after a second interim analysis, with 103 of 157 participants (65.6%) completing the study. The registry primary outcome analysis was restricted to participants who completed 52 weeks of treatment. The comparator was placebo plus as-needed anti-VEGF injections rather than a fixed-interval anti-VEGF regimen. Statements here are drawn from the full publication and the registry record.

X82-OPH-102 evaluated oral vorolanib (X-82), not the intravitreal insert, in 35 participants across 6 dose cohorts of 3 to 10 participants, without a control arm or masking. Efficacy outcomes were reported only for the 25 participants (71%) who completed 24 weeks, and 6 participants (17%) discontinued because of adverse events attributed to X-82, so the efficacy estimates are subject to attrition bias. Its relevance to this report is the systemic adverse event profile of vorolanib at oral exposures, including transaminase elevations. The study was funded by Tyrogenex, and 3 authors were Tyrogenex employees.