FDA awards orphan drug, rare pediatric disease designations to ABO-101 for PH1

The FDA has granted an orphan drug designation (ODD) and rare pediatric disease designation (RPDD) to ABO-101 for the treatment of patients with primary hyperoxaluria type 1 (PH1), Arbor Biotechnologies announced in a news release.¹

Preclinical data on ABO-101 were presented last year.

PH1 is a rare, genetic kidney disease characterized by the overproduction of oxalate, which can lead to kidney stones, kidney damage, and eventual kidney failure. ABO-101 is an investigational liver-targeting gene editing therapeutic intended to be a one-time treatment for PH1, according to the company. The therapy is designed to reduce expression of the HAO1 gene in the liver and thus decrease oxalate production.

In December 2024, the FDA accepted an investigational new drug application for ABO-101 to initiate the phase 1/2 redePHine trial of the therapy in patients with PH1.

The phase 1/2 trial is expected to launch in the first half of 2025. The study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ABO-101 in adult and pediatric patients with PH1. The design of the study will be shared at the 20th Congress for the International Pediatric Nephrology Association in Cape Town, South Africa later this month.

“ABO-101 receiving rare pediatric disease and orphan drug designations from the FDA for the potential treatment of PH1 underscores the urgent need for novel treatment options,” said Dan Ory, MD, Chief Medical Officer of Arbor Biotechnologies, in the news release.¹ “As Arbor advances ABO-101 into the clinic with the initiation of the redePHine Phase 1/2 clinical study, these designations reinforce the potential of ABO-101 to deliver lasting disease modification as a first-in-class gene editing therapy for PH1.”

ODD and RPDD are granted to drugs and biologics that are intended to treat serious, life-threatening diseases that affect fewer than 200,000 patients (ODD) or children under the age of 18 (RPDD). Under the designation, the development process for ABO-101 can benefit from exemptions from application fees and eligibility to receive a pediatric priority review voucher following a potential FDA approval of the therapy.

Preclinical data on ABO-101

Preclinical data on ABO-101 were presented last 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.”

References

1. Arbor Biotechnologies announces FDA Orphan Drug and Rare Pediatric Disease Designations Granted to ABO-101 for the treatment of primary hyperoxaluria type 1 (PH1) and upcoming presentations at the 20th Congress of the International Pediatric Nephrology Association (IPNA). News release. Arbor Biotechnologies Inc. Published online and accessed February 5, 2025. https://arbor.bio/arbor-biotechnologies-announces-fda-orphan-drug-and-rare-pediatric-disease-designations-granted-to-abo-101-for-the-treatment-of-primary-hyperoxaluria-type-1-ph1-and-upcoming-presentations-at-the-20t/

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 February 5, 2025. 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. AccessedFebruary 5, 2025. https://www.asn-online.org/education/kidneyweek/2024/program-abstract.aspx