EyeBio presents positive data on Restoret from AMARONE trial for DME and wet AMD

United-Kingdom-based Eyebiotech Limited (EyeBio) released 12-week data from the phase 1b/2a AMARONE trial, a first-in-human study evaluating Restoret, its lead retinal disease candidate, for the treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (wet AMD).

Let’s start with Restoret.

Introduced by EyeBio in March 2023, Restoret (EYE103) is a tetravalent, tri-specific antibody that operates as an agonist of the Wingless-related integration site (Wnt) signaling pathway.

Give me a quick refresher on this pathway, please.

This pathway is a group of signal transduction pathways beginning with proteins that pass signals into a cell through cell surface receptors.

In standard biology, the Wnt pathway plays a key role in developing and maintaining retina vasculature and the blood retinal barrier (BRB). When it’s disrupted, the endothelial cell barrier function is as well—leading to possible fluid leakage into the retina.

The result: increased levels of vascular endothelial growth factor (VEGF) in retinal conditions such as DME and wet AMD.

Gotcha. So how does Restoret work?

The antibody is delivered via intravitreal (IVT) injections for retinal vascular diseases with leakage (wet AMD and DME) as well as familial exudative vitreoretinopathy (FEVR).

Restoret has been designed to remove the leakage in these retinal diseases by forcing the Wnt pathway to restore and maintain the BRB.

Significance?

Through its activation of the Wnt pathway, Restoret has the potential to fulfill unmet medical needs in patients with DME and wet AMD.

Alrighty, now talk about this study.

The multicenter, open-label, Anti-permeability Mechanism and Age-Related Ocular Neovascularization Evaluation (AMARONE) trial (NCT05919693) is split into two parts:

• Part 1
  • Multiple-ascending dose (MAD) safety study (n = 12)
    • Four doses of Restoret between four cohorts (n = 3 for each)
      • Low
      • Low-mid
      • Mid-High
      • High
• Part 2
  • Dose-finding, single-masked comparative safety and preliminary efficacy study (n = 80)
    • Naïve DME monotherapy: medium and high doses
    • Naïve DME combination therapy (Restoret + aflibercept 2 mg): medium and high doses
    • Experienced wet AMD combination therapy (Restoret + aflibercept 2 mg): medium and high doses

All 92 participants (aged 50+) in both parts would receive a 12-week regimen of Restoret via IVT administration.

And the outcome measures?

Two outcomes are being measured, each evaluated for 3 months:

• Primary: adverse events (AEs)
• Secondary: best-corrected visual acuity (BCVA)

Now the findings.

Per EyeBio, Restoret was well-tolerated, with no reports of drug-related AEs or serious AEs, as well as intraocular inflammation (IOI).

DME patients (n = 26) receiving Restoret monotherapy demonstrated a BCVA mean improvement of +11.2 letters and a mean reduction in retinal thickness of -143 microns (measured via optical coherence tomography [OCT]).

Wet AMD patients (n = 5) receiving Restoret in combination with aflibercept demonstrated similar outcomes, according to the company.

Meaning?

Overall, EyeBio reported: “The data demonstrated that multiple monthly doses of Restoret, as both monotherapy and in combination with aflibercept, were well-tolerated.”

Significance?

According to David R. Guyer, MD, EyeBio CEO, the first-in-human (FIH) data from 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.”

So what’s next?

Per Clinical Trials, the study is slated to conclude by December 2024. Stay tuned for an additional data readout!

These findings were 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 on February 8, 2024, at the Macula Society Meeting in Palm Springs, California.