EyeBio announces positive data from first-in-human Ph1b/2a AMARONE trial of Restoret for DME, DVAMD

(Image Credit: AdobeStock/filmmaster)

Eyebiotech Ltd announced the presentation of Week 12 data from its first-in-human Phase 1b/2a AMARONE trial (NCT05919693) 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 on February 8, 2024, at the Macula Society Meeting in Palm Springs, California.

The company noted in its news release¹ that the Week 12 data from AMARONE demonstrated 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 µm, as measured by optical coherence tomography (OCT).

Moreover, according to the news release, 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.

Wykoff pointed out in the news release these data from AMARONE are “unique and impressive.”

“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,” he explained in the news release. “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.”

David R. Guyer, MD, CEO of EyeBio, said the company was pleased with the data.

“We are thrilled to be sharing first-in-human data from the Restoret development program,” he said in the news release. “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.”

Tony Adamis, MD, chief scientific officer of EyeBio, said the data demonstrates the potential to be able to help patients.

“Retinal diseases impact millions of people worldwide, and so we need to continue to innovate to help drive better outcomes for these patients,” Adamis said in a news release. “There is a great deal of preclinical evidence that agonizing the Wnt pathway in the retina results in reduction in vascular leakage, and so it is very gratifying to generate the first clinical evidence that validates this pathway in the eye.”

About the AMARONE clinical trial

According to EyeBio, 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).

The company noted that 4 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 NVAMD received Restoret in combination with aflibercept 2 mg every month for three months. All patients were followed for 12 weeks from their first dose.¹

Moreover, EyeBio noted in its news release the quality control of the trial database and data cleaning were successfully performed by IDDI/EyeBio. Of note, one participant had their end of study visit erroneously substituted for their safety extension injection visit, which was corrected. Another participant’s final visual acuity measurement was felt to be erroneous by the Principal Investigator (PI) on 11/20/23 (35 letters vs. 53 letters at month 2).

Because the patient had noted subjective improvement of their vision and the PI had observed clinical improvement on OCT and exam, the company noted the PI felt the recorded vision loss was not medically plausible. He brought the subject back for recheck 4 days later (after Eylea) on 11/24/23, at which time the patient’s visual acuity was restored to 59 letters. The PI corrected the final visit input to that measured on 11/24/23, which he felt was accurate and documented with a note to file.¹

About Restoret

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.¹

Reference:

1. EyeBio Announces Positive Visual, Anatomic and Safety Data from First-in-Human Ph1b/2a AMARONE Trial of Restoret at Macula Society Annual Meeting. www.businesswire.com. Published February 13, 2024. Accessed February 13, 2024. https://www.businesswire.com/news/home/20240212626117/en/EyeBio-Announces-Positive-Visual-Anatomic-and-Safety-Data-from-First-in-Human-Ph1b2a-AMARONE-Trial-of-Restoret-at-Macula-Society-Annual-Meeting

‌