Two-year safety and exploratory efficacy of AT845 gene replacement therapy for late onset Pompe disease: FORTIS, a phase 1/2 open-label clinical study


Clinical Trials

Poster Number: M238


Rezan Sahinkaya, MD, University of California Irvine, Nicola Longo, MD, PhD, University of Utah, Mark Walzer, PhD, Astellas Gene Therapies, Achim Steup, Dipl.-Stat, Astellas Pharma Global Development, Julie Coats, PT, Astellas Gene Therapies, Chieri Hayashi, MD., PhD., Astellas Pharma Global Development, INC., Jordi Diaz-Manera, MD, PhD, John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle-Upon-Tyne, UK

Pompe disease is a rare, autosomal recessive disease caused by a deficiency of lysosomal acid alpha-glucosidase (GAA), leading to the accumulation of glycogen resulting in damage to skeletal and cardiac muscles. AT845 (AAV8-eMCK-hGAA) is a gene therapy in clinical development for late onset Pompe disease (LOPD) that expresses the human GAA (hGAA) gene specifically in muscle tissues. FORTIS (NCT04174105) is an ongoing phase 1/2, multicenter, open-label, ascending dose, first-in-human clinical trial to determine the safety and tolerability and exploratory efficacy of AT845 in adults with LOPD. So far 5 participants have received a one-time intravenous infusion of AT845 at either the 3×10^13 vg/kg (n=2) or 6×10^13 vg/kg (n=3) dose level. We present data up to 2 years of follow-up for the first 4 participants dosed. Infusions were generally well-tolerated. Three of four participants developed transient, steroid responsive transaminitis that was mild to moderate and deemed possibly related to AT845. A grade 2 peripheral sensory neuropathy event was reported in one of four participants who received the 6×10^13 vg/kg dose and was designated as a serious adverse event (SAE) due to medical significance. All four participants showed evidence of AT845 vector transduction in the muscle and urine glucotetrasaccharide (Glc4) remained relatively stable even after withdrawal of ERT in 3 out of 4 patients through 1-year post treatment. Currently, 3 of 4 participants have withdrawn from ERT at 10, 17, and 24 weeks following AT845 infusion, and those participants were still off of ERT as of their 24-month follow-up. Analysis of functional outcomes through 2-years post-treatment is ongoing and will be presented as available. This study is funded by Astellas Gene Therapies.