Twelve-month results from the Phase 2 PAVIA trial of EYP-1901 (Duravyu; EyePoint Pharmaceuticals) for nonproliferative diabetic retinopathy (NPDR) showed promising signs of disease control, despite the trial not meeting its primary endpoint. Although the study did not achieve a 2-step-or-greater improvement on the Diabetic Retinopathy Severity Scale (DRSS), patients treated with EYP-1901 maintained stable or improved disease through 12 months following a single injection, said David Almeida, MD, MBA, PhD, an investigator for the PAVIA trial, at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Salt Lake City, Utah.
EYP-1901 is a bioerodible insert, delivered via a single intravitreal injection, containing vorolanib, a tyrosine kinase inhibitor that blocks VEGF activity. Subjects in PAVIA with moderately severe to severe NPDR were randomized into a 2 mg dose, 3 mg dose, or sham arm. As previously reported, at 6 months EYP-1901 demonstrated positive top-line results in PAVIA, showing a statistically significant improvement in the percentage of patients with a 2-or-more-step improvement in the DRSS score compared to sham.
“At 6 months, we see a trend of greater than 1 step improvement, which is best for the higher dose,” said Dr. Almeida, who is a consultant to EyePoint. “If you look at ‘stable no change,’ it's best for the higher dose. For 2-step improvement, it trends very nicely for both the 2 mg and 3 mg dose. So we're seeing good treatment effect there.”
However, the new data showed that the treatment effect dropped off after about 9 months. “The implant wore off. There's nothing left,” explained Dr. Almeida. “That's what that's telling us. So, we can see that a dose of EYP-1901 lasts about 9 months, and by 12 months that dose effect is gone.”
Notably, he said, the treatment was well tolerated, with no new safety concerns. This reinforces the favorable safety profile previously observed in trials of EYP-1901 for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).
Dr. Almeida said that EyePoint will use what it has learned about the implant’s durability as it prepares for a phase 3 trial in NPDR. “We likely have a treatment effect on the on the outcome of DRSS change, but we’ll need a bigger trial to actually look at it,” he said. That is in the planning stage, and could possibly start in 2026, he said.
EYP-1901 is currently being evaluated as a treatment for nAMD in the phase 3 LUCIA and LUGANO clinical trials, which are currently enrolling. EyePoint recently reported positive top-line data from the VERONA trial assessing EYP-1901 in DME. RP