EyeBiotech Ltd recently revealed week 12 data from its first-in-humans phase 1b/2a AMARONE trial of Restoret in patients with treatment-naïve diabetic macular edema (DME) and treatment-naïve neovascular age-related macular degeneration (nAMD). Restoret is an investigational, tri-specific Wnt agonist antibody that aims to eliminate leakage in vascular diseases by activating the Wnt pathway to both restore and maintain the blood-retinal barrier. The data was presented at the annual meeting of the Macula Society, February 7-10 in Palm Beach, California.
Patients with DME (n=26) received Restoret as monotherapy, manifesting a mean improvement in best-corrected visual acuity (BCVA) of +11.2 EDTRS letters and a mean reduction in retinal thickness of -143 µm, 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.
“These data from AMARONE are unique and impressive,” stated Charles C. Wykoff, MD, PhD, who presented the data at the Macula Society. “While anti-VEGF monotherapies have proven valuable, many patients still do not achieve optimal outcomes and there remains substantial unmet need for therapeutics with alternative mechanisms of action that can improve outcomes for patients with exudative retinal diseases including diabetic macular edema and wet macular degeneration. While early data thus far, it is exciting to see these meaningful anatomic and visual improvements using this differentiated and fascinating Wnt agonist, especially in the absence of VEGF inhibition.”
The Phase 1b/2a AMARONE (Antipermeability Mechanism and Age-Related Ocular Neovascularization Evaluation) clinical trial (NCT05919693) is a multicenter, 2-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 Restoret (EYE103) in participants with DME and nAMD. Four increasing doses of Restoret were tested sequentially in cohorts of 3 patients each during the MAD portion, and the 3 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 3 months, while patients with nAMD received Restoret in combination with aflibercept 2mg every month for 3 months. All patients were followed for 12 weeks from their first dose.
“We are thrilled to be sharing first-in-human data from the Restoret development program,” said David R. Guyer, MD, chief executive officer of EyeBiotech. “The AMARONE trial represents the first-ever clinical use of a Wnt pathway agonist to address retinal disease, and we are encouraged by the preliminary safety and efficacy data we’ve seen thus far.” NRP