AVROBIO Announces 100% Kidney Substrate Reduction at 12 Months Post-Gene Therapy in First Patient Dosed with plato Gene Therapy Platform in Fabry Disease Phase 2 Trial - Seite 2

Patient 4 is the first in the trial treated using AVROBIO’s proprietary plato gene therapy platform, which includes a state-of-the-art lentiviral vector, a personalized conditioning regimen with precision dosing and an automated, closed manufacturing process intended to deliver potent and consistent drug product from manufacturing sites worldwide at commercial scale.

“The complete clearance of Gb3 substrate in kidney tissue, coming on top of strong results from the first evaluable kidney biopsy in this trial, is very exciting,” said Mark Thomas, M.D., the lead investigator in the FAB-GT trial, a clinician in the department of nephrology at Royal Perth Hospital and a clinical professor at the University of Western Australia Medical School. “Along with the reduction in plasma lyso-Gb3 observed across patients in this trial, which has been sustained up to 2.5 years so far, a massive drop in kidney substrate has the potential to substantially improve outcomes over ERT – the current standard of care. Fabry disease is a serious and life-shortening condition for many patients that requires lifelong fortnightly ERT infusions, with life-limiting symptoms manifesting throughout the body and brain, and we urgently need options to halt, prevent or reverse progression of the disease.”

Two of four FAB-GT trial participants had evaluable kidney biopsies. As previously reported, the kidney biopsy for Patient 1 showed an 87% reduction, effective clearance of Gb3 inclusions per PTC compared to baseline.

Additional Fabry disease clinical data: Continued durability across multiple biomarkers and functional cardiac measurements

In addition to the kidney biopsy, AVROBIO reported updated data suggesting generally stable and sustained plasma and leukocyte alpha-galactosidase A (AGA) enzyme activity and a corresponding reduction in toxic plasma lyso-Gb3 in patients across the Phase 1 and FAB-GT trials of AVR-RD-01. To date, four patients have been dosed in the Phase 2 FAB-GT trial and five patients have been dosed in the fully enrolled Phase 1 trial.

New aggregated data across all cardiac measures for the FAB-GT patients show patients continue to exhibit stable cardiac structure and function at 12 months post-gene therapy, which is notable given that people living with Fabry disease often experience progressive left ventricular hypertrophy and fibrosis, leading to reduced cardiac function.