Aurion Biotech announced topline data from its Phase 1/2 clinical trial (CLARA) of AURN001, an allogeneic cell therapy product candidate for the treatment of corneal edema secondary to corneal endothelial dysfunction.
AURN001 is a combination cell therapy product candidate comprised of allogeneic human corneal endothelial cells (neltependocel) and a rho kinase inhibitor (Y-27632). AURN001 is intended to be administered to the anterior chamber of the eye as a one-time procedure, the company said in a press release.
The CLARA Phase 1/2 clinical trial (NCT06041256) is a prospective, multi-center, randomized, double-masked, parallel-arm dose-ranging clinical trial designed to assess the safety, tolerability, and efficacy of AURN001 for the treatment of corneal edema secondary to corneal endothelial dysfunction. Ninety-seven subjects were randomized at US and Canadian sites to each of the following five arms:
- AURN001: 1.0 × 106 neltependocel + 100 μM Y-27632 (high cell dose)
- AURN001: 5.0 × 105 neltependocel + 100 μM Y-27632 (medium cell dose)
- AURN001: 2.5 × 105 neltependocel + 100 μM Y-27632 (low cell dose)
- 100 μM Y-27632
- 1.0 × 106 neltependocel
At baseline across all arms, the mean age was 71.4 years, with 55% being female subjects. Baseline mean BCVA was 53.5 letters, using the Early Treatment Diabetic Retinopathy Standard (ETDRS) visual acuity test (20/85 Snellen), and CCT was 676.6 microns.
The primary endpoint was the proportion of responders with a >15-letter improvement (>3-line gain) from baseline in BCVA at 6 months. Key secondary endpoints included (1) change from baseline in BCVA and in CCT at 6 months and; (2) safety and tolerability.
For the primary endpoint, a dose-dependent response was observed in the three AURN001 arms, with a statistically significant improvement in the high-dose AURN001 arm (50% of responders, p=0.020), as compared to the Y-27632-only arm (14.3%).
A key secondary endpoint, change in BCVA at 6 months, showed a statistically significant improvement for the high-dose AURN001 arm (p=0.002), as compared to the Y-27632-only arm (using the full analysis set population (LOCF, LS mean2)). Additionally, a dose response was observed in the three AURN001 arms.
For the key secondary endpoint, change in CCT at 6 months, there was a statistically significant improvement for the high-dose AURN001 arm (p=0.012), as compared to the Y-27632-only arm (using the full analysis set population (LOCF, LS Mean)).
Separately, an improvement in patient-reported quality of life, assessed using the Visual Function Questionnaire (VFQ-25), was noted with the greatest benefit being seen in the high-dose AURN001 arm.
Doses from all five treatment arms were generally well tolerated with favorable safety profiles. There was no dose relationship observed in frequency of types of adverse events (AEs). There were no ocular serious adverse events (SAEs) reported and two non-ocular SAEs (hip fracture and femur fracture). The most frequently reported (>3%) ocular TEAEs were ocular hypertension (9.3%), conjunctival hemorrhage (5.2%), eye pain (4.1%), and cystoid macular edema (3.1%) and the most frequently reported non-ocular TEAE was COVID-19 (3.1%).
“We are thrilled with the topline results of the CLARA trial,” said Michael Goldstein, MD, MBA, president and chief medical officer of Aurion Biotech. “We were especially pleased that in the high-dose AURN001 arm at 6 months, there was a statistically significant improvement in the primary endpoint. Based on these findings, combined with the generally favorable safety profile in the CLARA trial, we look forward to bringing the high dose of AURN001 forward into our proposed Phase 3 pivotal trials.”
Greg Kunst, chief executive officer of Aurion Biotech, also 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.”
According to the company, topline data from the CLARA study follows Aurion Biotech’s announcement in June 2024 that the FDA granted AURN001 both Breakthrough Therapy Designation (BTD) and Regenerative Medicine Advanced Therapy (RMAT) designation, and Aurion’s commercial launch of its cell therapy in Japan, under the trade name Vyznova, in September 2024.
1 Although the study was not powered to show statistical significance, descriptive statistical analyses are provided in this topline readout.
2 LOCF: Last Observed Carry Forward statistical analysis, LS Mean: Least Squares Mean statistical analysis
3 JAMA Ophthalmology. 2016;134(2):167-173. doi:10.1001/jamaophthalmol.2015.4776.