Duravyu

Wet (neovascular) age-related macular degeneration (AMD) is the late neovascular form of AMD. The AAO estimates that about 80% of people with AMD have the non-neovascular form, yet the neovascular form accounts for nearly 90% of severe visual acuity loss (20/200 or worse) from AMD. The estimated annual incidence of neovascular AMD in White US adults aged 50 years or older is 1.8 per 1,000, and an estimated 168,400 people in the United States had new-onset neovascular AMD in 2018. In 2019, an estimated 1.49 million US adults aged 40 years or older (crude prevalence 0.94%) had late-stage AMD (choroidal neovascularization and/or geographic atrophy); globally, 196 million people were projected to have AMD in 2020 and 288 million in 2040.

Without treatment, eyes lose a mean of 2.7 lines of visual acuity by 12 months and 4 lines by 24 months, and the proportion with visual acuity worse than 20/200 rises from 19.7% at baseline to 75.7% by 3 years. With anti-VEGF therapy, scar developed in 480 of 1,059 eyes (45.3%) by 2 years in CATT, and in routine US practice the mean visual acuity gain at 1 year was 0.95 letter after a mean of 7.3 injections.

The humanistic burden includes depressive symptoms in 42.04% of 547 participants presenting for treatment (CES-D-10) and time trade-off utility values that fall from 0.89 at 20/20 to 20/25 to 0.40 at counting fingers to light perception in the better-seeing eye. The economic burden is concentrated in intravitreal anti-VEGF drugs: 2024 Medicare Part B spending, across all indications, was $2.37 billion for aflibercept 2 mg, $1.92 billion for faricimab, and $0.67 billion for aflibercept 8 mg. Mean annual societal ophthalmic costs were $39,910 in participants with visual loss compared with $6,116 in those with good vision, and direct nonmedical costs, primarily caregiver costs, made up 67.1% of the costs in participants with visual loss. Each treatment visit took a mean of 90 minutes in clinic and almost 12 hours including travel and recovery, 24.8% of caregivers in a UK survey required time off work, and 11.6% of treated participants in the IRIS Registry were lost to follow-up within 12 months.

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.

No price, product-specific sales forecast, budget impact model, cost-effectiveness analysis, or health technology assessment has been published for the vorolanib intravitreal insert (DURAVYU, EYP-1901), and no Institute for Clinical and Economic Review assessment of neovascular AMD therapies was identified. The product is investigational: the first phase 3 trial (LUGANO) did not meet its primary non-inferiority endpoint in the full dataset, the second (LUCIA) is expected to report in the fourth quarter of 2026, and EyePoint plans a potential NDA submission in the first half of 2027. EyePoint describes wet AMD and DME together as a "$15B+ global market opportunity" and states that it may need pharmacoeconomic studies to secure coverage and reimbursement.

The budget effect would depend mainly on the insert's price relative to the anti-VEGF injections it displaces and on the number of injections avoided. In LUGANO, treatment burden was reduced by 42% versus on-label aflibercept 2 mg, which the company stated "translates to two fewer injections on average" through week 56, and 54% of participants receiving the insert needed no supplemental injection through week 56. The comparator budget is concentrated in Medicare Part B: in 2024, fee-for-service Medicare spent $3.0 billion on Eylea and Eylea HD (329,500 users; $9,200 per user) and $1.9 billion on Vabysmo (173,300 users; $11,100 per user). By billing code, 2024 Part B spending was $2.37 billion for aflibercept 2 mg, $666 million for aflibercept 8 mg, $1.92 billion for faricimab, and $162 million for bevacizumab across all indications. A U.S. cost-utility model used CY2024 national payments of $125.28 per intravitreal injection (CPT 67028) and $157.64 per follow-up office visit, costs that recur with each injection visit.

Models of other durable anti-VEGF options indicate that savings from fewer injections depend on price and on the comparator. The ranibizumab port delivery system, the approved sustained-delivery comparator, cost more than bevacizumab injections in all scenarios and required 10.8 ranibizumab or 9.3 aflibercept injections to break even with 1 refill; it was cost effective versus ranibizumab injections at 1 year ($75,497 per QALY) but not at 5 years ($304,108 per QALY). Faricimab was dominant over aflibercept 2 mg in a 5-year U.S. payer model (22.6 vs 34 injections), with results most sensitive to acquisition prices. In a U.S. payer budget impact model of brolucizumab for a 1-million-member plan, the annual budget effect ranged from a saving of $94,170 to an increase of $824,696 depending on the dosing regimen assumed. Managed care stakeholders reported that many or most payers require off-label bevacizumab first, and a cost-neutral pricing analysis in a single-payer setting found that first-line use of newer agents required price reductions of 84% to 98% relative to bevacizumab. Budget impact for the vorolanib intravitreal insert therefore cannot be estimated from public data as of September 2026.

• Status: the vorolanib intravitreal insert 2.7 mg (DURAVYU, EYP-1901) is investigational and not approved by the FDA. No price, labeled indication, or labeled dosing exists. EyePoint plans an NDA submission in the first half of 2027, provided that results of the second phase 3 trial (LUCIA), expected in the fourth quarter of 2026, are positive.
• Current care: approved anti-VEGF agents are given by in-office intravitreal injection every 4 to 16 weeks, or every 20 weeks for aflibercept 8 mg after 1 year of successful response, with ongoing monitoring. Real-world visual gains are smaller than in trials, 11.6% of treated participants in the IRIS Registry were lost to follow-up within 12 months, and 2024 Medicare Part B spending on aflibercept 2 mg, aflibercept 8 mg, and faricimab totaled $4.95 billion across all indications.
• Efficacy: in LUGANO (432 participants), the insert did not meet its primary non-inferiority endpoint for BCVA change versus aflibercept 2 mg every 8 weeks in the full dataset. Non-inferiority was shown only in an ad hoc analysis that excluded 9 of 211 insert participants. The sponsor reported a 42% reduction in treatment burden (a mean of 3.1 compared with 5.3 injections after loading through week 56). In the phase 2 DAVIO 2 trial, single insert doses met non-inferiority for BCVA at weeks 28 and 32 in previously treated participants.
• Safety: in LUGANO, conjunctival hemorrhage, vitreous floaters, retinal hemorrhage, and neovascular AMD adverse events were more frequent with the insert, while intraocular inflammation and retinal detachment each occurred in 0.5% of both arms; serious and systemic adverse event data have not been released. In the DAVIO 2 registry results, the 3,090 µg arm had higher rates of study eye visual acuity reduced, vitreous floaters, serious endophthalmitis, and systemic hypertension than the aflibercept arm.
• Evidence limitations: LUGANO results are preliminary sponsor reports without peer review; the comparator was fixed aflibercept 2 mg every 8 weeks rather than aflibercept 8 mg, faricimab, or treat-and-extend dosing; all 76 registered LUGANO sites were in the United States; and no patient-reported outcome data have been released.
• Economic information: no budget impact model, cost-effectiveness analysis, or health technology assessment of the insert has been published. Budget impact will depend on the insert's price relative to the anti-VEGF injections it replaces and on the number of injections avoided.
• Pending information: LUCIA topline results (fourth quarter of 2026), LUGANO subgroup analyses at retina meetings beginning in September 2026, the final LUGANO analysis, and FDA review.