Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration

PurposeTo evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan–vascular endothelial growth factor (VEGF) receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy.DesignPhase 1, multicenter, prospective, open-label, dose-escalation trial.ParticipantsPatients with wAMD and evidence of prior anti-VEGF therapy response.MethodsPatients received a single intravitreal injection of EYP-1901.Main Outcome MeasuresThe primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates.ResultsSeventeen patients enrolled in the 440 μg (3 patients), 1030 μg (1 patient), 2060 μg (8 patients), and 3090 μg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline (CFB) in BCVA was –3.7 letters and –5.4 letters at 6 and 12 months. Mean CFB in CST was +1.7 μm and +2.3 μm at 6 and 12 months. Reduction in treatment burden was 76% and 72% at 6 and 12 months. Of 16 study eyes, 13, 9, and 6 were injection-free up to 3, 6, and 12 months.ConclusionIn the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing Phase 2 and planned Phase 3 trials to assess efficacy and safety.