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
AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced a 100% reduction, or complete clearance, of toxic substrate in the kidney biopsy of the first patient dosed with the plato gene therapy platform in the ongoing Phase 2 FAB-GTi clinical trial of AVR-RD-01, an investigational ex vivo lentiviral gene therapy for Fabry disease. Kidney substrate reduction is the trial’s primary efficacy endpoint and has previously been used by the U.S. Food and Drug Administration (FDA) in evaluating and approving treatments for Fabry disease.
The company also announced six-month data from the first patient dosed in the Phase 1/2 trial of AVR-RD-02, an investigational ex vivo lentiviral gene therapy for Gaucher disease type 1, showing plasma chitotriosidase and the toxic metabolite lyso-Gb1 – key biomarkers of Gaucher disease – had both dropped sharply below the patient’s baseline levels achieved on enzyme replacement therapy (ERT) before gene therapy was administered. Additionally, all three cystinosis patients in the investigator-sponsored Phase 1/2 trialii of AVR-RD-04 show strong data across multiple measures and remain off cysteamine pills and eye drops, with trial enrollment completion expected this year.
“We are thrilled to begin the new year with this update, which adds to the breadth of strong clinical data we’ve reported across our leading lysosomal disorder pipeline of single-dose gene therapies,” said Geoff MacKay, president and CEO of AVROBIO. “With 13 patients dosed across three clinical programs, we have observed sustained and potentially transformative improvements in key biomarkers and functional metrics, with data from our Fabry disease program out 3 ½ years after dosing. Additionally, enrollment activities for our Fabry disease trial are accelerating, giving us added confidence in our efforts to meet our goal of having dosed a cumulative 30 patients across all our clinical programs by the end of the year. With this strong momentum, we look forward to clarifying the regulatory pathway with regulatory agencies.”
The data will be presented this week at the 17th annual WORLDSymposium, an annual scientific meeting dedicated to lysosomal disorders, held virtually Feb. 8-12, 2021. The presentations and posters are available online for WORLD attendees on the conference website.
FAB-GT biopsy data: 100% reduction of kidney substrate at 12 months in first patient dosed with plato gene therapy platform
Gb3 is a fatty substrate that accumulates in the cells of Fabry disease patients and can result in damage to multiple organs, including the kidneys, heart and CNS. The kidney biopsy for Patient 4 in the Phase 2 trial showed a reduction from an average of 4.0 globotriaosylceramide (Gb3) inclusions per peritubular capillary (PTC) at baseline to zero inclusions per PTC one year after dosing, a 100% reduction (p<0.0001). This assessment was made by two blinded pathologists who independently scored 99 digital images of the sectioned kidney from the 12-month biopsy. Every image scored zero inclusions.