PAVIA: Duravyu Misses Primary Phase 2 Endpoint in Diabetic Retinopathy

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The phase 2 trial failed to show improvement of ≥2-DRSS levels with the vorolanib intravitreal insert in patients with non-proliferative diabetic retinopathy.

PAVIA: Duravyu Misses Primary Phase 2 Endpoint in Diabetic Retinopathy | Image Credit: New England Eye Center

Jay Duker, MD

Credit: New England Eye Center

Topline results from the phase 2 PAVIA trial show the vorolanib intravitreal insert (DURAVYU™) missed its pre-specified primary endpoint, but displayed biologic effects, in patients with non-proliferative diabetic retinopathy (NPDR).1

Notably, the trial did not identify an improvement of ≥2 Diabetic Retinopathy Severity Scale (DRSS) by week 36 after vorolanib intravitreal insert injection. However, according to Eyepoint Pharmaceuticals, the treatment exhibited stable or improved disease severity with reduced rates of NPDR progression and a favorable safety and tolerability profile.

“Although the trial did not meet the pre-specified primary endpoint, we are encouraged that DURAVYU continues to be well-tolerated and appears to reduce rates of NPDR progression at nine months,” Jay Duker, MD, chief executive officer of EyePoint Pharmaceuticals, said in a statement.1 “We plan to analyze the full twelve-month data once it is available to gain the clarity needed to assess the future of DURAVYU as a potential treatment for NPDR.”

Previously known as EYP-1901, DURAVYU™ has been conditionally accepted by the US Food and Drug Administration (FDA) as the proprietary name for the vorolanib intravitreal insert.1 The treatment delivers vorolanib, a selective and patent-protected tyrosine kinase inhibitor (TKI) formulated in a solid bioerodible insert using the company’s proprietary sustained-release Durasert E™ technology.

In December 2023, topline results from the phase 2 DAVIO 2 trial showed EYP-1901 achieved all primary and secondary endpoints in treating wet age-related macular degeneration (AMD).2 These data, showing a statistical, non-inferior change in visual acuity to aflibercept, helped advance the wet AMD program into phase 3 pivotal trials.

PAVIA, a phase 2, randomized, controlled trial, recruited 77 patients with moderately severe to severe NPDR and assigned them to one of two doses of vorolanib, or a sham injection.1 Vorolanib intravitreal insert can be delivered with a routine intravitreal injection in the physician’s office, similar to currently available anti-vascular endothelial growth factor (VEGF) treatments.

Upon analysis, topline interim results from PAVIA revealed 86% of patients in the vorolanib 3 mg arm and 80% of those in the 2mg arm experienced stable or improved NPDR at 9 months, compared with 70% in the control arm.

Further analysis showed no patient in the 3 mg arm and 5% in the 2 mg arm experienced worsened ≥2-step DRSS scores at 9 months, compared with 10% in the control arm. Meanwhile, 5% of patients in the 3 mg arm and 0% in the 2 mg arm achieved a ≥2-step improvement in DRSS score at 9 months, compared with 5% in the control arm.

The data demonstrated a continuation of the favorable safety and tolerability profile of the vorolanib intravitreal insert, with no treatment-related ocular or systemic serious adverse events reported in the trial. There were no observed cases of endophthalmitis or retinal vasculitis (occlusive or non-occlusive) as well.

In the news release, EyePoint Pharmaceuticals announced they remain on track to initiate the first pivotal, phase 3 pivotal trial in wet AMD (LUGANO) in the second half of 2024, with the second global phase 3 pivotal trial in wet AMD (LUCIA) expected to follow. A readout of topline data from the phase 2 trial in diabetic macular edema (VERONA) is anticipated for Q1 of 2025.

“We remain confident that DURAVYU has the potential to change the treatment paradigm as a maintenance therapy for wet AMD patients based on the highly positive data seen in DAVIO 2, the largest intravitreal sustained release TKI study in wet AMD to date,” Duker added.1

References

  1. EyePoint Pharmaceuticals announces topline data from the Phase 2 Pavia Trial of DURAVYUTM in non-proliferative diabetic retinopathy. EyePoint Pharmaceuticals. May 6, 2024. Accessed May 6, 2024. https://investors.eyepointpharma.com/news-releases/news-release-details/eyepoint-pharmaceuticals-announces-topline-data-phase-2-pavia.
  2. Iapoce C. EYP-1901 for wet AMD achieves primary endpoint in davio 2 trial. HCP Live. December 7, 2023. Accessed May 6, 2024. https://www.hcplive.com/view/eyp-1901-wet-amd-achieves-primary-endpoint-davio-2-trial.
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