Charles C. Wykoff, MD, PhD: Phase 1b/2a Results on Restoret for DME, nAMD

At the 128th Annual American Academy of Ophthalmology (AAO) Meeting, Charles C. Wykoff, MD, PhD, director of clinical research at Retina Consultants of Texas, presented first-time results on Restoret (EYE103) from the Phase 1b/2a AMARONE trial, targeting diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD).

The innovative molecule, developed as a Wnt pathway agonist, aims to stabilize the blood-retinal barrier, offering an alternative to traditional anti-vascular endothelial growth factor (VEGF) therapies, which target vascular permeability. According to Wykoff, Restoret’s mechanism allows for enhanced retinal health through activation rather than inhibition, potentially requiring lower doses for efficacy.

“Across the Phase 1b/2a extension studies associated with AMARONE, we saw Restoret remained safe and well-tolerated across 123 injections,” Wykoff told HCPLive. “Most notably, we saw these structural and functional improvements in a DME population treated without VEGF inhibitors, a very unique approach.” 

Restoret mimics Norin, a protein naturally present in the eye, to activate a Wnt pathway receptor, Frizzled-4, which maintains the structural integrity of retinal blood vessels. In AMARONE, which included patients with DME and nAMD, Restoret demonstrated strong safety outcomes, with no drug-related adverse effects or inflammation across 123 total injections. Patients with DME received Restoret alone, while patients with nAMD received it in combination with aflibercept.

Efficacy results were positive across both patient groups, with patients with DME receiving Restoret monotherapy experiencing an average visual acuity improvement of 11.2 letters and a reduction in central subfield thickness (CST) from approximately 500 to 350 µm by Week 12. In the nAMD cohort, Restoret and aflibercept combined therapy led to a mean visual acuity gain of 6.8 letters and substantial reductions in CST, achieving below 300 µm within one month.

Following these promising findings, Restoret is progressing to the pivotal Brunello trial comparing Restoret monotherapy against anti-VEGF treatments in DME patients with central vision impairment.

“This is a two-year multi-center randomized trial in which Restoret monotherapy is being compared directly to anti-VEGF therapy,” Wykoff told HCPLive. “This trial is actively recruiting now, so I’m looking forward to seeing more data from Restoret in the years to come.”

Disclosures: Relevant disclosures for Wykoff include Annexon, Apellis, Eyebiotech, Genentech, Regeneron, and others.

References

_{Do DV. Restoret (EYE103) for the Treatment of Diabetic Macular Edema and Neovascular AMD: First-time Extended Results From the AMARONE Phase 1b/2a Clinical Trial. Presented at the American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}