Aurion Biotech Evaluating Combination Cell Therapy Product AURN001 as Alternative to Corneal Transplant in Phase 1/2 ABA-1, CLARA Clinical Trial

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In honor of Healthy Vision Month, CGTLive® took a closer look at the clinical trial design for this novel treatment.

Aurion Biotech’s AURN001 (marketed as Vyznova in Japan), a combination cell therapy and small molecule product that remains investigational in the United States, is currently being evaluated for the treatment of corneal edema secondary to corneal endothelial dysfunction in the phase 1/2 ABA-1, CLARA clinical trial (NCT06041256).1 In honor of Healthy Vision Month, observed annually in the month of May by the patient and clinician communities, CGTLive® has decided to take a closer look at the clinical trial design for this novel treatment.

AURN001 consists of allogeneic human corneal endothelial cells, referred to as “neltependocel”, and Y-27632, a small molecule drug that inhibits Rho-associated, coiled-coil containing protein kinase. AURN001, which is delivered to the eye via intracameral injection, is meant to be a 1-time treatment for certain corneal conditions.

ABA-1, CLARA, which is a multicenter, randomized, double-masked, dose-ranging study, is taking place at sites in both the US and Canada. Participants in the trial are assigned in parallel to 1 of 5 arms. In 3 of the 5 arms, participants are treated with AURN001, with each arm corresponding to treatment with either a low, medium, or high dose of neltependocel within the combination product. In 1 of the 5 arms, participants receive neltependocel alone at a dose equivalent to that used in the high dose AURN001 arm. In the remaining arm of the study, patients are treated with Y-27632 alone.

On April 8, 2024, Aurion announced that the first Canadian patient had received AURN001 in the trial, with treatment of US patients having begun earlier on in October 2023.1,2 Soon after, on April 30, 2024, Aurion Biotech announced that ABA-1, CLARA had completed enrollment, with 97 patients having been randomly assigned to the aforementioned treatment arms and dosed across centers in the US and Canada.3 According to the clinicaltrials.gov page, which was most recently updated on April 5, 2024, the study had been recruiting at sites in Arkansas, California, Georgia, Indiana, Kansas, Minnesota, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Dakota, Texas, Virginia, Washington, British Columbia, and Ontario. The trial, which began on October 18, 2023, has an estimated primary completion date of October 2024 and an estimated study completion date of October 2025.

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“Aurion Biotech is delighted that both enrollment and dosing in our phase 1/2 trial are now complete, and that it happened more rapidly than we expected,” Michael Goldstein, MD, MBA, the president and chief medical officer of Aurion Biotech, said in an April 30, 2024, statement.1 “We enrolled and dosed subjects in 6 months, which speaks to the deep interest among physicians and patients for our allogeneic cell therapy, as well as the potentially large, unmet need for our elegant, minimally invasive procedure to treat this sight-threatening disease.”

ABA-1, CLARA’s primary end point measures whether patients have achieved a 15 letter improvement (3-line gain) or greater in best-corrected visual acuity (BCVA) from baseline at 6 months posttreatment. Currently, the clinicaltrials.gov page does not list any secondary end points for the study.

The trial recruited patients aged 18 years to 99 years who had been diagnosed with corneal edema secondary to corneal endothelial dysfunction; a condition that would typically necessitate full- or partial-thickness endothelial keratoplasty. Participants were also required to have a BCVA between 65 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (0.4 LogMAR or approximate 20/50 Snellen equivalent) and 5 ETDRS letters (1.6 LogMAR or approximate 20/800 Snellen equivalent).

Patients with preoperative corneal epithelial, subepithelial, or stromal scarring or other opacity in the study eye that was paracentral/central and visually significant, but that was not suspected to be secondary to corneal endothelial disease with the potential to improve from treatment, were excluded from participation in ABA-1, CLARA. Furthermore, patients with any history of any ocular disease other than corneal endothelial dysfunction that could impact the trial’s vision or safety assessments were not eligible to participate.

“We are thrilled that were able to enroll and dose patients in the CLARA phase 1/2 trial in just 6 months—much faster than we anticipated,” Greg Kunst, MBA, the CEO of Aurion Biotech, said in a statement issued to CGTLive on May 24, 2024. “We believe it’s due to high interest from corneal specialists and their enthusiasm to advance the development of our cell therapy. On the strength of the clinical data package presented to FDA for our phase 1/2 trial, the endpoint for BCVA is 6 months versus what is typically a 12-month endpoint. We look forward to sharing topline results of this trial in early 2025.”

Aurion has developed AURN001 with the intention of treating multiple indications that currently require corneal transplant. Notably, the therapy was previously approved for the treatment of bullous keratopathy of the cornea in Japan in March 2023.4

In April 2023, CGTLive spoke with Arnaud Lacoste, PhD, the chief scientific officer of Aurion Biotech, about AURN001 and its potential to address unmet needs. He explained the rationale behind developing an alternative to corneal transplant, explaining that it is a very invasive and complex procedure and that the outcomes are often imperfect, making it a less–than ideal option for patients and ophthalmic surgeons alike. Lacoste also pointed out that because of global shortages of donor corneal tissue, many patients with corneal dystrophies in other parts of the world cannot receive treatment for their condition at all.

"Worldwide, having a cell therapy as a replacement for corneal transplantation addresses the gap between the demand for treatment and tissue availability...” Lacoste told CGTLive in the interview. "[W]e have about 1 cornea available for about 70 needed. With our cell therapy, we can take 1 tissue from 1 donor and generate many doses. And that will eventually enable us to bridge the gap between the demand for treatment and the supply. And because our cell therapy, again, is allogeneic—so it’s universal—from that 1 donor, we can treat any patients, regardless of their HLA type. This is very important because, again, it speaks to the impact that this cell therapy will have worldwide.”

REFERENCES
1. Aurion Biotech announces first Canadian subject dosed in phase 1/2 clinical trial. News release. Aurion Biotech. March 28, 2024. Accessed May 27, 2024. https://aurionbiotech.com/aurion-biotech-announces-first-canadian-subject-dosed-in-phase-1-2-clinical-trial/
2. Aurion Biotech announces first subject dosed in U.S. Phase 1/2 clinical trial. Aurion Biotech. October 24, 2024. Accessed May 27, 2024. https://aurionbiotech.com/aurion-biotech-announces-first-subject-dosed-in-us-clinical-trial/
3. Aurion Biotech announces completion of enrollment in phase 1/2 clinical trial. News release. Aurion Biotech. April 30, 2024. Accessed May 27, 2024. https://aurionbiotech.com/aurion-biotech-announces-completion-of-enrollment-in-phase-1-2-clinical-trial/
4. Aurion Biotech receives approval from Japan’s PMDA for new drug application. News release. Aurion Biotech. March 23, 2023. Accessed May 27, 2024. https://aurionbiotech.com/aurion-biotech-receives-approval-from-japans-pmda-for-new-drug-application/
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