AVROBIO, Inc. announced that it is shifting its portfolio priorities to focus on other clinical-stage programs and extending its cash runway into the first quarter of 2024. The company is deprioritizing its Fabry disease program due to several factors, including new clinical data showing variable engraftment patterns from the five most recently dosed Phase 2 FAB-GT patients which would significantly extend the program's development timeline, as well as an increasingly challenging market and regulatory environment for Fabry disease. New data from Phase 2 FAB-GT clinical trial show variable engraftment: The aggregated data from the five most recently dosed FAB-GT patients showed variable engraftment patterns.

Data from three of the five patients showed both a reduction to near baseline levels in alpha-galactosidase A (AGA) enzyme activity in leukocytes and plasma, and a reduction in vector copy number (VCN) in whole blood, potentially suggesting resistance to persistent engraftment of the genetically modified cells observed at three to nine months post infusion of AVR-RD-01. Based on its investigation, the company believes, due to the large degree of heterogeneity in Fabry disease, that in some cases there may be intrinsic resistance to engraftment related to the unique underlying pathophysiology of untreated Fabry disease, potentially caused by the persistently stressed vascular endothelium. The company also has reviewed potential procedure-related factors and conditioning parameters, including the possible impact, in the context of untreated Fabry disease, of a previous clinical trial protocol amendment for the five recently dosed patients which prolonged the conditioning agent washout period by up to 48 hours.

Safety data from all nine adult patients dosed in the Phase 2 FAB-GT trial and the five adult patients dosed in the investigator-sponsored Phase 1 trial show no adverse events (AEs) or serious adverse events (SAEs) related to drug product AVR-RD-01, as of the most recent data cut-off date. The company will stop enrollment for the FAB-GT clinical trial and continue monitoring the previously dosed patients for a total of 15 years as required by regulators.