Aurion Biotech announces topline results from Phase 1/2 trial of AURN001 for corneal edema

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Aurion Biotech Inc. has released topline data from its Phase 1/2 CLARA clinical trial (NCT06041256) evaluating AURN001, an allogeneic cell therapy product candidate for the treatment of corneal edema secondary to corneal endothelial dysfunction.

According to the company, AURN001 combines allogeneic human corneal endothelial cells (neltependocel) and a rho kinase inhibitor (Y-27632). The therapy is designed to be administered as a one-time procedure into the anterior chamber of the eye.

The company noted that corneal endothelial dysfunction is a sight-threatening condition that affects millions worldwide. When corneal endothelial cells die or degrade, they do not regenerate in vivo, leading to corneal edema and vision loss. While corneal transplants are a current treatment option, they are complex, invasive, and limited by donor tissue availability—with only one healthy donor cornea estimated for every 70 diseased eyes. This highlights a significant unmet need for minimally invasive, effective therapies that are not restricted by donor supply.

The CLARA trial is a prospective, multi-center, randomized, double-masked, parallel-arm, dose-ranging clinical trial conducted in the U.S. and Canada. The study aimed to evaluate the safety, tolerability, and efficacy of AURN001 in patients with corneal edema due to corneal endothelial dysfunction.

A total of 97 participants were randomized across five treatment arms:

• High cell dose: 1.0 × 10⁶ neltependocel + 100 μM Y-27632
• Medium cell dose: 5.0 × 10⁵ neltependocel + 100 μM Y-27632
• Low cell dose: 2.5 × 10⁵ neltependocel + 100 μM Y-27632
• Y-27632 only: 100 μM Y-27632
• Cells only: 1.0 × 10⁶ neltependocel

The company noted that at baseline, the mean age across all groups was 71.4 years, with 55% of participants being female. Mean best-corrected visual acuity (BCVA) was 53.5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart (approximately 20/85 Snellen), and mean central corneal thickness (CCT) was 676.6 microns.

The primary endpoint was the proportion of responders achieving a ≥15-letter improvement (≥3-line gain) in BCVA at 6 months. A dose-dependent response was observed in the AURN001 treatment arms, with statistically significant improvement in the high-dose group:

• High-dose AURN001 arm: 50% of responders (p=0.020)
• Y-27632-only arm: 14.3% of responders

For the key secondary endpoint, change in BCVA at 6 months, the high-dose AURN001 arm demonstrated a statistically significant improvement (p=0.002) compared to the Y-27632-only arm. A dose response was similarly observed across the 3 AURN001 arms.

According to the company, change in CCT at 6 months, another key secondary endpoint, also showed significant improvement in the high-dose AURN001 arm (p=0.012) compared to the Y-27632-only arm.

Additionally, patient-reported quality of life, assessed using the Visual Function Questionnaire (VFQ-25), showed the greatest improvement in the high-dose AURN001 group.

All treatment arms demonstrated favorable safety profiles, with no dose-dependent trends in adverse events (AEs). No ocular serious adverse events (SAEs) were reported. Two non-ocular SAEs (hip fracture and femur fracture) occurred.

The most frequently reported (>3%) ocular treatment-emergent adverse events (TEAEs) were:

• Ocular hypertension: 9.3%
• Conjunctival hemorrhage: 5.2%
• Eye pain: 4.1%
• Cystoid macular edema: 3.1%

The most frequently reported non-ocular TEAE was COVID-19 (3.1%).

Michael Goldstein, MD, MBA, president and chief medical officer of Aurion Biotech, said the company was pleased with the topline results of the CLARA trial.

“We were especially pleased that in the high-dose AURN001 arm at six months, there was a statistically significant improvement in the primary endpoint,” he said in a statement. “Based on these findings, combined with the generally favorable safety profile in the CLARA trial, we look forward to advancing the high dose of AURN001 into our proposed Phase 3 pivotal trials.”

Greg Kunst, CEO of Aurion Biotech, added, “We believe that today’s news is another important step forward in the clinical development of our investigational allogeneic cell therapy, AURN001, to help restore vision. We look forward to presenting full results from the CLARA trial at future medical conferences.”

The CLARA results come on the heels of significant milestones for Aurion Biotech, including the FDA’s June 2024 designation of AURN001 as both a Breakthrough Therapy and a Regenerative Medicine Advanced Therapy (RMAT). In addition, the company is set to commercially launch its cell therapy in Japan under the trade name Vyznova in September 2024.