Astellas Announces Positive Safety and Tolerability of AT845 Gene Therapy in Adults with Late-Onset Pompe Disease

News on February 14, 2022 /BioValleyBIOON/ -- Astellas recently announced interim safety data from the Phase 1/2 FORTIS trial of gene therapy AT845 for the treatment of late-onset Pompe disease (LOPD).AT845 is an investigational adeno-associated virus (AAV) gene replacement therapy designed to deliver a functional α-glucosidase (GAA) gene, enabling the direct expression of acid α-glucosidase (GAA) in patients' muscle cells. AT845 has the potential to become a best-in-class therapy.

FORTIS is an ongoing multi-center, open-label, dose-escalation, first-in-humanClinical Trial, aimed to determine the safety and tolerability of AT845 in adult patients with LOPD. Enrolled patients received a single peripheral intravenous infusion of AT845, followed by frequent monitoring of safety, clinical, and biochemical endpoints over one year, including GAA activity and protein levels in muscles, as well as long-term safety monitoring over four years. The primary endpoints of the trial are safety and tolerability, along with efficacy measures, including changes in muscle GAA protein expression and enzyme activity relative to baseline. Secondary endpoints evaluated improvements in respiratory function, endurance, and quality of life metrics.

As of the data cutoff date of December 3, 2021, four patients were enrolled in the trial, with two patients infused at a dose of 3×10E13 vg/kg (Cohort 1) and two patients infused at a dose of 6×10E13 vg/kg (Cohort 2). The reported data include interim safety and tolerability assessments, as well as up to 24 weeks of follow-up for the two patients in Cohort 1 and preliminary data for the two patients in Cohort 2.

Data Show That AT845 Was Well-Tolerated in Four Adult LOPD Patients Treated. In Cohort 1, AT845 Demonstrated Encouraging Safety During the 24-Week Follow-Up Period After Infusion in Two Patients. Importantly, as of the Data Cutoff, No Serious Adverse Events Were Reported Post-Infusion in Any of the Four Patients. One Patient Experienced Elevated Transaminases, Which Was Considered a Common Immune-Mediated Treatment Response Given the Timing of Onset After Dosing, Occurrence During Steroid Tapering, and Reversal Upon Steroid Restart. These Safety Data Are Encouraging, and the Program Will Continue to Enroll Patients.

Pompe disease (Pompe disease, PD) is a rare and severe autosomal recessiveGeneticsMetabolic disease characterized by progressive muscle degeneration, caused by GAA gene mutations that interfere with the production or function of the GAA protein. GAA is responsible for glycogen metabolism, and dysfunction or absence of this protein leads to glycogen accumulation, primarily in skeletal and cardiac muscles, thereby causing damage to tissue structure and function. Currently, the only approved treatment for Pompe disease is enzyme replacement therapy (ERT), which is administered intravenously every two weeks and relies on tissue uptake of GAA from plasma.

AT845 is a muscle-targeted gene replacement therapy using the AAV8 capsid serotype, featuring a cardiomyocyte and skeletal muscle-specific promoter, delivering a functional copy of the GAA gene. AT845 is being developed for the treatment of late-onset Pompe disease (LOPD), effectively transducing the functional GAA gene and directly delivering it to the tissues affected by the disease, expressing GAA in skeletal and cardiac muscles. (Bioon.com)

Source of the original text:Astellas Announces Positive Safety Data from the FORTIS Study of AT845 in Adults with Late-Onset Pompe Disease