Arbor Biotechnologies has dosed the first patient in its Phase 1/2 rephine trial of ABO-101, a CRISPR gene editing therapy for primary hyperoxaluria type 1 (PH1). No serious adverse events or dose-limiting toxicities were observed within 28 days post-dosing. The trial’s safety board recommended dose escalation, which continues at the Mayo Clinic. Additional sites in the UK and EU are planned.
This first-in-human dosing marks Arbor’s entry into the clinic and signals the growing momentum behind in vivo gene editing for rare diseases. ABO-101, designed as a one-time therapy, targets the •HAO1• gene to reduce oxalate production in the liver. This approach contrasts with current PH1 treatments, which rely on lifelong siRNA therapies or, in severe cases, combined liver-kidney transplants. The trial’s rapid activation through an accelerated pathway at the Mayo Clinic underscores the urgency to address the unmet need in this debilitating condition.
Arbor’s focus on a single-dose intervention reflects a broader industry push toward curative treatments that reduce the burden of chronic care. This aligns with both patient preferences and payer pressures to contain healthcare costs. However, the long-term safety and efficacy of gene editing remain under scrutiny, and regulators will carefully evaluate the durability of response and potential off-target effects in this and other similar trials.
The redePHine trial’s design – a global, open-label dose escalation study – will provide initial data on safety, tolerability, pharmacokinetics, and pharmacodynamics. Preliminary efficacy signals will be crucial for Arbor to secure further investment and potentially expedite the regulatory pathway. The inclusion of pediatric patients later in the trial highlights the company’s intention to address PH1 across the age spectrum, broadening the potential market. Further global expansion into UK and EU sites is planned.
The success of ABO-101 hinges on demonstrating a sustained reduction in oxalate levels, a key marker of disease progression. Long-term follow-up will be critical to confirm the therapy’s potential to prevent kidney damage and avoid the need for transplantation. The trial will be closely watched as a test case for the feasibility and safety of CRISPR-based therapies for metabolic disorders, particularly those affecting the liver. Arbor’s strategy of leveraging an established LNP delivery system from Acuitas Therapeutics may mitigate some of the manufacturing and delivery challenges often associated with gene therapies. This study will also contribute valuable data to the ongoing debate about the long-term monitoring and management of patients who receive gene editing interventions.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
