Aro Biotherapeutics has achieved a significant milestone in rare disease drug development by completing enrollment in its Phase 1b clinical trial of ABX1100, an investigational siRNA therapy for late-onset Pompe disease (LOPD). The trial is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of ABX1100 in patients with LOPD who are currently receiving enzyme replacement therapy (ERT).
Novel Therapeutic Approach Addresses Unmet Medical Need
"While rapid enrollment in the Phase 1b ABX1100 clinical trial brings us closer to establishing proof of concept for GYS1 inhibition as a therapeutic approach, it also shows the overwhelming physician and patient desire for new treatments driven by the significant unmet clinical need," said Purnanand Sarma, Ph.D., chief executive officer of Aro Biotherapeutics.
ABX1100 represents a fundamentally different approach to treating Pompe disease compared to current standard of care. The investigational therapy is a first-in-class Centyrin–siRNA conjugate that inhibits expression of glycogen synthase 1 (GYS1), the enzyme responsible for glycogen production. This targeted substrate reduction strategy addresses the underlying pathophysiology of the disease rather than simply replacing the deficient enzyme.
Addressing Disease Burden and Treatment Limitations
People living with LOPD have a genetic deficiency in the enzyme that breaks down glycogen, a stored form of sugar used for energy. As a result, glycogen accumulates in muscle tissue, causing cellular damage and organ dysfunction that present as muscle impairment, weakness, and disability that can eventually progress to death from respiratory failure.
"Pompe disease is a highly debilitating disease that significantly impairs the patient's strength and independence, as available therapies are quite onerous," added Ozlem Goker-Alpan, M.D., president of Lysosomal and Rare Disorders Research and Treatment Center, and an investigator on the study. "ABX1100 is designed to potentially reduce the burden of Pompe disease and deliver meaningful improvements to patients and their families, using a completely novel treatment modality."
Current enzyme replacement therapy requires intravenous infusions that can last as long as 6 hours, multiple times a month, creating significant treatment burden for patients despite limited efficacy.
Innovative Centyrin Technology Platform
Aro is developing a pipeline of tissue-targeted siRNA medicines using a proprietary protein technology called Centyrins, which are small proteins engineered for exceptional efficiency, versatility, and safety. ABX1100 specifically comprises a CD71 receptor-binding Centyrin conjugated to a short-interfering RNA (siRNA) that specifically interferes with expression of GYS1 messenger RNA (mRNA), thereby reducing levels and overall activity of the GYS1 enzyme in muscle tissues.
Trial Design and Regulatory Status
When combined with ERT, and as a monotherapy, ABX1100 has shown significant activity in preclinical models. The Phase 1b trial aims to validate those findings in patients with LOPD and evaluate the potential of ABX1100 to improve patient outcomes.
All patients enrolled in the trial received one dose of ABX1100 on Day 1 and a booster dose on Day 29, and will be monitored through 20 weeks to assess safety and preliminary therapeutic activity. Analysis of the results will inform the design of later-phase clinical studies of ABX1100.
ABX1100 has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration, providing regulatory advantages for this rare disease indication. The trial is registered at ClinicalTrials.gov under identifier NCT06109948.
