Duravyu (vorolanib intravitreal insert)

The vorolanib intravitreal insert (DURAVYU, EYP-1901) is investigational and not approved by the FDA. LUGANO randomized 432 participants 1:1 to the insert 2.7 mg (2 inserts in 1 injection) every 6 months, first given at week 8 after aflibercept loading doses, or to aflibercept 2 mg every 8 weeks; supplemental aflibercept was permitted in both arms. The primary endpoint, non-inferiority (margin -4.5 letters) for mean change in BCVA from baseline averaged over weeks 52 and 56, was not met in the full dataset, and the full-dataset treatment difference and confidence interval have not been reported in text. Nine of 211 participants (4.3%) in the insert arm, and none of 216 in the aflibercept arm, lost 15 or more letters from causes the sponsor attributed to conditions other than wet AMD (geographic atrophy, 6; glaucoma, 2; retinal detachment, 1). Non-inferiority was shown only in an ad hoc analysis that excluded these 9 participants: the insert arm gained 3.5 letters and the aflibercept arm 5.9 letters (difference -2.4 letters; nominal p = 0.0096). Baseline history of glaucoma in the study eye was 11.4% in the insert arm and 5.9% in the aflibercept arm, and 0.5% of the LUGANO aflibercept arm lost 15 or more letters, compared with 7.7% of the aflibercept arm in DAVIO 2. A prespecified analysis of supplement-free participants (113 insert participants, 54%) reported non-inferiority, with a difference of -1.8 letters (nominal p = 0.0035).

After loading doses through week 56, participants received a mean of 3.1 injections in the insert arm and 5.3 in the aflibercept arm, a 42% reduction in treatment burden (nominal p < 0.0001) against a maximum possible reduction of 60%. In the insert arm, 76% of participants were supplement-free through week 32 and 54% through week 56, and the mean difference in central subfield thickness versus aflibercept at week 56 was 4 µm. All LUGANO results are topline sponsor reports labeled preliminary and pending final analysis, and none has been peer reviewed. LUCIA, an identical trial with 475 participants, is expected to report topline data in the fourth quarter of 2026; the sponsor states that learnings from LUGANO were included in the LUCIA analysis plan and plans an NDA submission in the first half of 2027, provided LUCIA results are positive.

Through week 56, among 211 participants receiving the insert and 221 receiving aflibercept, ocular adverse events in the study eye that were more frequent with the insert included conjunctival hemorrhage (11.4% and 5.0%), vitreous floaters (9.0% and 3.6%; all mild or moderate per the sponsor), neovascular AMD (7.1% and 1.4%), retinal hemorrhage (4.7% and 1.8%), retinal edema (2.8% and 0.9%), and visual impairment (2.4% and 0.0%). Cataract (4.3% and 5.4%), increased intraocular pressure (3.8% and 3.2%), intraocular inflammation (0.5% in each arm), and retinal detachment (0.5% in each arm) occurred at similar rates, and endophthalmitis was reported only as less than 1% in both arms. The sponsor reported no insert migration into the anterior chamber, retinal vasculitis, or severe intraocular inflammation, and discontinuation through week 56 of 6% in each arm. Serious and systemic adverse event data have not been released.

DAVIO 2 randomized 161 previously treated participants (156 in the full analysis set) to a single insert dose of 2,060 µg or 3,090 µg at week 8 or to aflibercept 2 mg every 8 weeks. For the primary endpoint (BCVA change averaged over weeks 28 and 32), the registry reports least-squares mean differences versus aflibercept of -0.12 letters (95% CI, -2.48 to 2.24) for 2,060 µg and -0.31 letters (95% CI, -2.63 to 2.02) for 3,090 µg, with both lower limits above the -4.5-letter margin. At week 56, mean BCVA change was 1.1 letters with aflibercept, 0.3 letters with 2,060 µg, and -1.9 letters with 3,090 µg, and 82.7%, 42.6%, and 46.2% of participants had received no supplemental aflibercept.

In the registry safety results, the 3,090 µg arm had higher rates than the aflibercept arm of study eye visual acuity reduced (8 of 52 participants, 15.38%, compared with 3 of 54, 5.56%), vitreous floaters (6 of 52, 11.54%, compared with 1 of 54, 1.85%), retinal hemorrhage (6 participants compared with 1), serious endophthalmitis (3 of 52, 5.77%, compared with 2 of 54, 3.70%), systemic hypertension (7 of 52, 13.46%, compared with 4 of 54, 7.41%), and serious systemic adverse events (9 of 52, 17.31%, compared with 6 of 54, 11.11%); 1 participant (1.92%) in the 3,090 µg arm also had serious non-infectious endophthalmitis. No endophthalmitis event was considered related to EYP-1901; events in the insert arms were attributed to the supplemental aflibercept injection procedure or the paracentesis for aqueous humor collection, or were not considered treatment related. Two deaths (4.00%) occurred in the 2,060 µg arm and none in the other arms. Sponsor presentations reported no EYP-1901-related ocular or systemic serious adverse events.

In the open-label phase 1 DAVIO trial (17 participants, single doses of 440 to 3,090 µg), no dose-limiting toxicity or ocular serious adverse event was observed; mean BCVA change was -1.8 letters at 6 months and -5.4 letters at 12 months, and treatment burden was 74% lower at 6 months and 71% lower at 12 months than in the pre-enrollment period. An oral formulation of vorolanib (X-82) was studied earlier in wet AMD, and its phase 2 APEX trial was stopped early because of gastrointestinal and hepatobiliary adverse events and fulfillment of the primary endpoint.

• Participants in the LUGANO insert arm receiving zero or one supplemental injection through week 32: 94% in the August 17, 2026 press release, compared with 96% in the August 2026 and September 2026 company presentations.
• DAVIO 2 primary endpoint difference versus aflibercept: -0.12 letters (2,060 µg) and -0.31 letters (3,090 µg) as least-squares differences in the registry, compared with -0.3 and -0.4 letters in the company topline release and Form 10-K.
• DAVIO 2 supplement-free rates: 65% and 64% up to 6 months in the Form 10-K, compared with 62.5% and 63.5% up to week 32 in the registry.
• DAVIO 2 full analysis set: participants who received at least 1 dose of study treatment in the registry, compared with participants who received both day 1 and week 8 treatments in company congress presentations.
• LUGANO analysis populations: 216 aflibercept participants in efficacy and baseline tables, compared with 221 in adverse event tables.