Breaking News: LUCIA Misses in Wet AMD — EyePoint Shifts to DME

Breaking news: EyePoint Pharmaceuticals announced this morning that LUCIA, the second pivotal Phase 3 trial of Duravyu (vorolanib, EYP-1901) for wet AMD, did not achieve the primary endpoint of statistical non-inferiority in mean change in BCVA versus on-label aflibercept. EyePoint is shifting resources away from its wet AMD program and re-focusing efforts on its DME program. John Kitchens, MD, and Scott Krzywonos break down the data — what the secondary endpoints showed, what the safety profile looked like across both trials, and what LUCIA means for TKIs as a class. The conversation closes with a look at why EyePoint still believes Duravyu has a future in DME, and what the COMO and CAPRI trials will need to show. Hosts: John Kitchens, MD, Scott Krzywonos Topics Covered LUCIA Topline Results Primary endpoint: not met. LUCIA did not achieve statistical non-inferiority in mean change in BCVA vs. aflibercept 2mg every eight weeks in 475 patients with wet AMD. Secondary endpoints met: 38% reduction in treatment burden vs. aflibercept (nominal p less than 0.0001); 52% of Duravyu eyes supplement-free through week 56; 71% received zero or one supplement through week 56. Visual improvement was demonstrated — the drug works biologically — but not to the margin required for non-inferiority. Both LUGANO and LUCIA showed the same pattern: durability and anatomic control with treatment burden reduction, but not the vision bar that a regulatory submission requires. Pooled safety: retinal hemorrhage 4.7% (Duravyu) vs. 1.5% (aflibercept); vitreous hemorrhage 2.3% vs. 0.0%; cataract rate comparable between arms. No increase in inflammation with redosing. What the LUGANO Pattern Means In LUGANO, nine patients in the treatment arm drove the primary endpoint miss — six with GA progression, one with a repaired retinal detachment, two with glaucoma. Whether LUCIA showed a similar subgroup pattern or a broader, more global finding was not addressed on the investor call. EyePoint says additional analyses of pooled LUGANO and LUCIA data are ongoing. John’s read: the hemorrhage signal is worth watching for TKIs broadly. Extended dosing intervals without close monitoring may allow lapse of disease control in patients prone to hemorrhage. Identifying those patients earlier — and either monitoring them more closely or switching agents — will be important as TKIs move toward approval. What It Means for TKIs Duravyu’s wet AMD failure does not close the book on TKIs. Axpaxli (Ocular Therapeutix) had a positive superiority study in SOL-1, albeit with an unusual study design that selected for highly responsive patients. What the EyePoint data add is real-world texture: TKIs produce durability and anatomic control, but the vision bar in wet AMD may be harder to clear than expected. The extended interval also raises monitoring questions that approval studies don’t fully answer. Understanding which patients tolerate 6-month dosing — and which don’t — may be essential before widespread clinical adoption. The DME Pivot EyePoint is refocusing resources on Duravyu in DME. The rationale: DME is a multifactorial, inflammatory disease where Duravyu’s mechanism may be more relevant than in wet AMD. The Phase 2 VERONA trial met its primary endpoint in DME with extended time to first supplemental injection. Two pivotal Phase 3 DME trials — COMO and CAPRI — are ongoing. Topline data expected Q4 2027. John’s observation: treatment burden reduction in working-age DME patients carries a different weight than in wet AMD — fewer injections means less time off work, which matters to patients and their employers. DME is also a more forgiving disease for subretinal hemorrhage and does not carry the same atrophy risk that complicated both wet AMD trials. Key Takeaways LUCIA missed its primary endpoint. EyePoint is winding down the wet AMD program and pivoting to DME. The wet AMD TKI chapter for Duravyu is all but closed. The secondary data confirm Duravyu’s biological activity — 52% supplement-free at week 56 — but biological activity and regulatory approval are not the same thing. TKIs as a class still have a future, but the hemorrhage and monitoring data from LUGANO and LUCIA may inform how Axpaxli is positioned if it reaches approval. COMO and CAPRI in DME read out Q4 2027. DME may be where the TKI mechanism ultimately finds its clinical home. Credits Production & Marketing: Laura Brown | Business Operations: Liz Hogan 🎧 Listen at RetinUp.com | Apple Podcasts | Spotify | YouTube