EYP-1901 Intravitreal Insert Noninferior to Aflibercept in Treating nAMD

EYP-1901, a bioerodible, sustained-release intravitreal insert delivering vorolanib, has indicated noninferiority to aflibercept in treating neovascular age-related macular degeneration (nAMD), achieving its primary endpoint in the DAVIO 2 trial. Notably, a single dose of EYP-1901 generated equivalent results in visual acuity compared to aflibercept Q8W over 6 months.1

Presented at the 43rd Annual Scientific Meeting of the American Society Retina Specialists in Long Beach, CA, by Jennifer Lim, MD, University of Illinois at Chicago, the DAVIO 2 study was a phase 2, multicenter, prospective, randomized, double-masked trial assessing efficacy and safety of EYP-1901 versus aflibercept in previously treated eyes with nAMD.1

The DAVIO 1 trial, published in April 2024, indicated the safety and efficacy of the EYP-1901 implant based on responses from 17 patients. No dose-limiting toxicity, ocular serious adverse events, or systemic adverse events were observed, and no evidence of ocular or systemic toxicity was observed related to either the EYP-1901 delivery technology or vorolanib itself. Only 1 severe treatment-emergent adverse event of worsening nAMD disease activity was noted, but was deemed unrelated to treatment.2

Investigators randomized patients with previously treated nAMD to either 1 injection of EYP-1901 2mg, 1 injection of EYP-1901 3mg, or aflibercept 2mg Q8W. All treatment arms were given 3 loading doses of aflibercept 2mg at day 1, week 4, and week 8, with EYP-1901 or sham injection administered at week 8. If prespecified best-corrected visual acuity (BCVA) and/or anatomic criteria were met, eyes in all groups could receive supplemental aflibercept injections.1

The primary endpoint for DAVIO 2 was mean change in BCVA from day 1 to week 28/32 on average. Investigators also noted secondary endpoints of safety, mean change in central subfield thickness (CST), BCVA through 56 weeks, and proportion of eyes without supplemental injections.1

Lin and colleagues included 156 eyes in the trial; 50 patients were randomized to EYP-1901 2mg, 52 patients to EYP-1901 3mg, and 54 patients to aflibercept 2mg Q8W. Mean baseline BCVA was 73.9, 74.9, and 73.4 letters in EYP-1901 2 mg, EYP-1901 3mg, and aflibercept 2mg Q8W, respectively.1

DAVIO 2 met its primary endpoint: mean (standard deviation [SD]) BCVA change from baseline at the average of month 7/8 was statistically noninferior between EYP-1901 2 and 3 mg and aflibercept 2 mg Q8W (mean [SD] letters +1 [6.4], +.9 [4.2], +1.3 [6.8], respectively; difference versus aflibercept of -.3 and -.4 letters, noninferiority margin -4.5 letters). Additionally, mean BCVA change from baseline in EYP-1901-treated eyes was similar to that of the overall population., indicating that supplemental injections did not drive visual outcomes.1

Investigators evaluated vision outcomes based on BCVA letters lost or gained at the primary endpoint. They noted similar proportions of eyes gaining ≥5, ≥10, and ≥15 letters for EYP-1901 2mg and 3mg as for aflibercept Q8W. Fewer eyes in the EYP-1901-treated arms had loss of ≥10 letters compared to aflibercept Q8W, and EYP-1901 maintained or improved vision in over 80% of patients. EYP-1901 was also well tolerated, with no related ocular or systemic serious adverse events.1

Ultimately, Lim and colleagues noted a similar outcome from a single EYP-1901 dose compared to aflibercept.

“In the DAVIO 2 trial, a single dose of EYP-1901 resulted in similar proportions of eyes with improvements in visual acuity as aflibercept Q8W over 6 months with vision maintained or improved in over 80% of patients,” Lim and colleagues wrote.1

References

1. Lim J, Ribeiro R. Vision Outcomes From the DAVIO 2 Trial: A Phase 2 Trial of EYP-1901 vs Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration. Abstract presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.

2. Patel S, Storey PP, Barakat MR, et al. Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration. Ophthalmol Sci. 2024;4(5):100527. Published 2024 Apr 9. doi:10.1016/j.xops.2024.100527