EyePoint Pharmaceuticals (Nasdaq: EYPT) reported a Phase III primary-endpoint miss for vorolanib (Duravyu) in wet age-related macular degeneration (wet AMD), after the LUGANO pivotal trial failed to demonstrate non-inferiority to aflibercept on visual acuity in the full analysis dataset. Favorable treatment-burden and safety results, together with a positive ad hoc analysis excluding nine patients, leave the program's planned 2027 NDA filing increasingly dependent on the second pivotal LUCIA trial.
LUGANO's primary endpoint measured change from baseline in best corrected visual acuity (BCVA), averaged across Weeks 52 and 56, against on-label aflibercept. EyePoint attributed the miss to nine of 211 Duravyu-treated patients who lost at least 15 letters for reasons the company said were unrelated to wet AMD, compared with no such cases in the aflibercept arm. Excluding those patients in an ad hoc analysis, Duravyu met the non-inferiority criterion with a nominal p-value of 0.0096.
EyePoint also argued that the aflibercept control arm overperformed historical benchmarks, citing comparable Phase III trials in which approximately 3–5% of aflibercept-treated patients lost at least 15 letters. The imbalance nevertheless leaves LUGANO without a successful prespecified primary analysis.
Secondary endpoints were more favorable. Duravyu reduced treatment burden by 42% versus on-label aflibercept, meeting the superiority threshold with a nominal p-value below 0.0001 and translating to approximately two fewer injections through Week 56. Some 76% of patients were supplement-free through Week 32 and 54% through Week 56, while 79% received no more than one supplemental injection through Week 56. A prespecified analysis among supplement-free patients showed non-inferior BCVA versus aflibercept.
Anatomic control was also maintained, with a mean central subfield thickness difference of four microns versus aflibercept at Week 56. No new safety signals emerged, including no retinal vasculitis, insert migration or free-floating drug particles, and no differences between groups in cataracts, intraocular pressure or intraocular inflammation.
Duravyu combines the small-molecule tyrosine kinase inhibitor vorolanib with EyePoint's bioerodible Durasert E intravitreal delivery technology. Vorolanib acts intracellularly to inhibit VEGF receptors and PDGFR, while EyePoint has also reported preclinical evidence of IL-6/JAK1 pathway inhibition. The insert is administered by standard intravitreal injection and designed to release drug for approximately six months, distinguishing it from repeatedly injected anti-VEGF biologics and surgically implanted sustained-delivery systems.