Aurion Biotech has announced positive topline results from its Phase 1/2 CLARA clinical trial evaluating AURN001 for corneal edema secondary to corneal endothelial dysfunction. The trial demonstrated statistically significant improvements in visual acuity and corneal thickness, suggesting a potential new treatment option for this sight-threatening condition.
The CLARA trial (NCT06041256) was a randomized, multi-center, double-masked study conducted in the U.S. and Canada. It included 97 participants randomized across five treatment arms to evaluate the safety, tolerability, and efficacy of AURN001. The treatment arms included varying doses of corneal endothelial cells (neltependocel) combined with a rho kinase inhibitor (Y-27632), corneal endothelial cells alone, and the rho kinase inhibitor alone.
Key Findings from the CLARA Trial
The primary endpoint of the trial was the proportion of responders achieving a ≥15-letter improvement (≥3-line gain) in best-corrected visual acuity (BCVA) at 6 months. The high-dose AURN001 arm (1.0 × 10⁶ neltependocel + 100 μM Y-27632) showed that 50% of patients achieved this improvement (p=0.020), compared to 14.3% in the Y-27632-only arm. Key secondary endpoints, including change in BCVA and central corneal thickness (CCT) at 6 months, also demonstrated statistically significant improvements in the high-dose AURN001 arm (p=0.002 and p=0.012, respectively) compared to the Y-27632-only arm.
According to Aurion Biotech, a dose-dependent response was observed across the three AURN001 treatment arms. The mean age across all groups was 71.4 years, with 55% of participants being female. Mean baseline BCVA was 53.5 letters (approximately 20/85 Snellen), and mean CCT was 676.6 microns.
Addressing Unmet Needs in Corneal Edema Treatment
Corneal endothelial dysfunction affects millions worldwide. When corneal endothelial cells die or degrade, they do not regenerate in vivo, leading to corneal edema and vision loss. Current treatment options, such as corneal transplants, are complex, invasive, and limited by donor tissue availability. It is estimated that there is only one healthy donor cornea for every 70 diseased eyes, highlighting a significant unmet need for minimally invasive, effective therapies that are not restricted by donor supply.
Dr. Zaina Al-Mohtaseb, a cataract, refractive, & cornea surgeon with Whitsett Vision Group, noted that current treatments like Descemet membrane endothelial keratoplasty (DMEK) involve challenging post-operative care and carry risks such as the need for additional procedures. AURN001 significantly reduces patient burden, requiring minimal post-operative positioning and offering a simpler recovery.
Safety and Future Directions
All treatment arms demonstrated favorable safety profiles, with no dose-dependent trends in adverse events (AEs). No ocular serious adverse events (SAEs) were reported. The most frequently reported ocular treatment-emergent adverse events (TEAEs) were ocular hypertension (9.3%), conjunctival hemorrhage (5.2%), and eye pain (4.1%).
"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," said Michael Goldstein, MD, MBA, president and chief medical officer of Aurion Biotech.
Aurion Biotech is also preparing to commercially launch its cell therapy in Japan under the trade name Vyznova in September 2024. The FDA has granted AURN001 both Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations.
