Enrollment complete in Phase 1b trial of ABX1100 for LOPD
Study to test treatment's safety and tolerability in adults
A Phase 1b clinical trial testing substrate reduction therapy ABX1100 in late-onset Pompe disease (LOPD) has completed enrollment, developer Aro Biotherapeutics said.
This part of the trial (NCT06109948) investigates the medication’s safety, tolerability, and pharmacological profile in adults with LOPD. ABX1100 is given by intravenous (into-the-vein) infusion.
“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,” Purnanand Sarma, PhD, CEO of Aro, said in a company press release.
In Pompe disease, mutations in the GAA gene lead to a toxic build-up of glycogen, a complex sugar molecule, inside cells. GAA codes for the acid alpha-glucosidase (GAA) enzyme, which normally breaks down glycogen. Enzyme replacement therapy (ERT), which aims to provide the body with a functional form of the GAA enzyme, is the mainstay Pompe treatment.
ABX1100 takes a different approach by targeting glycogen synthase (GYS1), an enzyme that allows muscle cells to produce glycogen.
‘Novel treatment modality’ aims to reduce burden
“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,” said Ozlem Goker-Alpan, MD, an investigator on the study and president of the Lysosomal and Rare Disorders Research and Treatment Center.
The investigational treatment contains a small interfering RNA (siRNA) molecule engineered to reduce the amount and activity of GYS1. To do so, the siRNA targets the GYS1 messenger RNA (mRNA), an intermediate molecule that carries information from DNA to serve as a template when producing the enzyme. In addition, ABX1100 has an engineered protein called centyrin to improve siRNA delivery to target cells.
In mouse studies, the therapy reduced GYS1 and glycogen levels in muscle cells. The company said the treatment shows benefits both alone and when combined with ERT. The Phase 1 trial seeks to validate those findings in people with LOPD and to see whether ABX1100 can improve patient outcomes.
In the first part of the Phase 1 trial, investigators tested ABX1100 in healthy adults.
In the 10 weeks following two infusions four weeks apart, GYS1 mRNA and protein levels in muscle samples decreased by about 70%. Although ABX1100 cleared rapidly from participants’ blood, it persisted in the muscles. The therapy was well tolerated, with no serious adverse events reported up to 85 days after treatment.
Phase 1b participants will also receive two doses of ABX1100 on days 1 and 29. Investigators will monitor safety and early signs of efficacy for 20 weeks. Aro hopes this will provide information to support the design of future clinical studies.
The U.S. Food and Drug Administration has granted ABX1100 orphan drug and rare pediatric disease designations. These statuses, intended for therapies that address rare disorders, are intended to expedite their development.
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