The DAVIO trial: a phase 1, open-label, dose-escalation study of a single injection of EYP-1901 (vorolanib in Durasert^® platform) demonstrating reduced treatment burden in wet age-related macular degeneration

Abstract

Purpose : Undertreatment of wet age-related macular degeneration (wAMD) with anti–vascular endothelial growth factor (anti-VEGF) therapies may account for a significant proportion of unsatisfactory visual outcomes in the real world. The DAVIO trial was a phase 1, multicenter, open-label, dose-escalation trial evaluating the safety of EYP-1901, a sustained-delivery therapy supplying the tyrosine kinase inhibitor (TKI) vorolanib in a bio-erodible form of Durasert^® given via intravitreal injection.

Methods : Previously treated eyes with wAMD received EYP-1901 with up to 48 weeks of follow-up. The primary endpoint was the rate of ocular and systemic adverse events. Secondary endpoints included best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements.

Results : Seventeen eyes received 440 µg (n=3), 1,060 µg (n=1), 2,060 µg (n=8), or 3,090 µg (n=5) of EYP-1901. Investigator-reported adverse events were mostly mild in nature and related to the intravitreal injection procedure; no reported adverse events were related to EYP-1901. The mean (standard deviation (SD)) change in BCVA from baseline was –2.5 (12.66) letters at 6 months and –4.1 (13.59) letters at 12 months, using the Early Treatment Diabetic Retinopathy Study (ETDRS) score. The mean (SD) change in OCT central subfield thickness (CST) from baseline was –3.4 (89.83) µm at 6 months and –2.8 (94.99) µm at 12 months. There was a 75% reduction in anti-VEGF treatment burden at 6 months and a 73% reduction at 12 months. After 1 injection of EYP-1901, 53% of eyes were supplemental anti-VEGF injection–free up to 6 months and 35% up to 12 months.

Conclusions : EYP-1901 had a favorable ocular and systemic safety profile at the doses evaluated. More than half of eyes treated with EYP-1901 demonstrated control of wAMD for up to 6 months after 1 treatment. Sustained delivery of vorolanib was achieved in this trial, and EYP-1901 will progress to a larger phase 2 clinical trial. The full 12-month study results will be presented along with an ad hoc analysis of eyes with no excess fluid on OCT at baseline.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.