FDA greenlights phase 1/2 trial of gene editing therapy for primary hyperoxaluria 1

The FDA has accepted an investigational new drug application for ABO-101 to initiate a phase 1/2 trial of the gene editing therapy in patients with primary hyperoxaluria type 1 (PH1), Arbor Biotechnologies announced in a news release.¹

Preclinical data on ABO-101 were presented earlier this year.

According to the company, ABO-101 is a liver-targeting gene editing therapeutic intended to be a one-time treatment for PH1. The therapy is designed to reduce expression of the HAO1 gene in the liver and thus decrease oxalate production.

The phase 1/2 trial, called redePHine, is expected to launch in the first half of 2025. Overall, the study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ABO-101 in adult and pediatric patients with PH1.

“We are thrilled to advance ABO-101 to the clinic as we believe it has the potential to be a first-in-class treatment for PH1, a rare disease with a high unmet need, and reinforces the promise of our precisely tailored gene editing approach,” said Dan Ory, MD, chief medical officer of Arbor Biotechnologies, in the news release.¹ “ABO-101 is supported by a strong suite of preclinical data demonstrating specific and durable in vivo editing of HAO1 and corresponding, therapeutically relevant reductions in urinary oxalate in PH1 disease models.”

Preclinical data on ABO-101

Preclinical data on ABO-101 were presented earlier this year at the American Society of Gene and Cell Therapy 27th Annual Meeting in Baltimore, Maryland and at the American Society of Nephrology (ASN) 2024 Kidney Week in San Diego, California. Overall, the data demonstrated the proof-of-pharmacology and efficacy of ABO-101 in non-human primates.^2,3

The investigators found that ABO-101 was able to specifically target the HAO1 gene and preserve genomic integrity following gene editing. According to the presentation at ASN Kidney Week, HAO1 gene editing was achieved in approximately 60% of whole liver tissue.³

In a preclinical model, in vivo editing of the HAO1 gene resulted in a therapeutically relevant reduction in urinary oxalate. Additionally, gene editing led to diminished glycolate oxidase enzyme activity and increased serum glycolate levels.

Specifically, HAO1 editing in 60% of whole liver tissue was correlated with a greater than 2 times increase in serum glycolate. These increases were dose-dependent, with increases in gene editing levels found to be associated with increases in serum glycolate levels and reductions in glycolate oxidase activity.

Multiple doses of ABO-101 also appeared to be well tolerated in the non-human primates.

Based on these findings, the authors concluded, “Taken together, these results provide in vivo proof of pharmacology for a gene editing approach and support further advancement of ABO-101 towards the clinic as a potential treatment for PH1.”

“The FDA approval of the ABO-101 IND marks a significant milestone for the hyperoxaluria community,” concluded Kim Hollander, executive director of The Oxalosis and Hyperoxaluria Foundation (OHF), in the new release.¹ “At OHF, we are committed to partnering with industry leaders to advance care, research, and patient-focused drug development for hyperoxaluria. Arbor’s innovative CRISPR-based approach represents a groundbreaking opportunity in genomic medicine, with the potential to transform the lives of patients with PH1.”

References

1. Arbor Biotechnologies announces FDA acceptance of IND application for ABO-101 for the treatment of primary hyperoxaluria type 1. News release. Arbor Biotechnologies Inc. Published online and accessed December 19, 2024. https://arbor.bio/arbor-biotechnologies-announces-fda-acceptance-of-ind-application-for-abo-101-for-the-treatment-of-primary-hyperoxaluria-type-1/

2. Arbor Biotechnologies presents data supporting clinical development of ABO-101 and robust potential of platform to enable therapeutic programs at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting. News release. Arbor Biotechnologies. May 9, 2024. Accessed December 19, 2024. https://arbor.bio/arbor-biotechnologies-presents-data-supporting-clinical-development-of-abo-101-and-robust-potential-of-platform-to-enable-therapeutic-programs-at-the-american-society-of-gene-and-cell-therapy-asgct/

3. Yan W, Ditommaso T, Kuefner M, et al. Development of ABO-101, a novel gene editing therapy for primary hyperoxaluria type 1. American Society of Nephrology (ASN) 2024 Kidney Week Meeting. October 23-27. San Diego, California. Abstract TH-OR88. Accessed December 19, 2024. https://www.asn-online.org/education/kidneyweek/2024/program-abstract.aspx