Eyebiotech Limited (EyeBio) has announced week 12 data from its first-in-human Phase 1b/2a AMARONE trial of Restoret in patients with treatment-naïve diabetic macular edema (DME) and treatment-naïve neovascular age-related macular degeneration (NVAMD).
The analysis was presented by Charles C. Wykoff, MD, PhD, Director of Research at Retina Consultants of Texas and Chairman of the Research and Clinical Trials Committee, Retina Consultants of America at the Macula Society Meeting in Palm Springs, California.
The presentation of Week 12 data from AMARONE demonstrated that Restoret was well-tolerated, with no drug-related adverse events, drug-related serious adverse events, or intraocular inflammation reported.
Patients with DME (n=26) received Restoret as monotherapy, manifesting a mean improvement in best-corrected visual acuity of +11.2 letters and a mean reduction in retinal thickness of -143 microns, as measured by optical coherence tomography (OCT). Similar outcomes were observed in patients with NVAMD (n=5), who received Restoret in combination with aflibercept. The data demonstrated that multiple monthly doses of Restoret, as both monotherapy and in combination with aflibercept, were well-tolerated.
The AMARONE trial represents the first ever clinical use of a Wnt pathway agonist to address retinal disease.
The Phase 1b/2a AMARONE (Anti-permeability Mechanism and Age-Related Ocular Neovascularization Evaluation) clinical trial is a multi-center two-part trial consisting of an open-label multiple ascending dose (MAD) safety study, and a single-masked comparative safety and preliminary efficacy study of intravitreal (IVT) Restoret (EYE103) in participants with diabetic macular edema (DME) and neovascular age-related macular degeneration (NVAMD).
Four increasing doses of Restoret were tested sequentially in cohorts of 3 patients each during the MAD portion, and the three highest doses were subsequently tested in a larger cohort of patients during the proof of concept portion of AMARONE.
Patients with DME received intravitreal Restoret monotherapy every month for three months, while patients with NVAMD received Restoret in combination with aflibercept 2mg every month for three months. All patients were followed for 12 weeks from their first dose.
Restoret is an investigational tri-specific Wnt agonist antibody designed to address urgent unmet medical need in patients with back-of-the-eye diseases. Restoret aims to eliminate leakage in vascular diseases by activating the Wnt pathway to both restore and maintain the blood-retinal barrier. The result of a breakthrough in protein engineering and manufacturing, Restoret may enable the clinical translation of the extensively studied Wnt pathway for the first time in the eye. Published research has shown that Wnt signaling in the retina plays a central role in the maintenance of vascular integrity, and defects in Wnt signaling cause retinal vascular leakage. Restoret has demonstrated activity in preclinical ophthalmic models, including validation in genetic models.