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Avrobio Stops Enrollment of Fabry Disease Gene Therapy Trial

January 4, 2022

Avrobio said it will stop enrollment for the clinical trial of its Fabry disease gene therapy to shift its priorities to other clinical-stage programs to extend its cash runway into the first quarter of 2024.

Photo: Geoff MacKay, president and CEO of Avrobio

The company said it 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.

Shares of Avrobio fell more than 30 percent in morning trading after the company made the announcement.

“Following steady progress in 2021, we have reset our corporate priorities and will extend our cash runway to strengthen our ability to deliver on the promise of our gene therapy programs,” said Geoff MacKay, president and CEO of Avrobio. “Powered by our proprietary plato gene therapy platform, we will focus our efforts on moving value driving clinical-stage programs forward in 2022, with data updates expected for our cystinosis and Gaucher disease type 1 programs, as well as regulatory interactions anticipated across multiple programs in our pipeline.

The company said previously reported data from 13 patients treated across its three clinical-stage programs have shown durable engraftment out 9 to 54 months. It is the new data from the five most recently dosed phase 2 FAB-GT patients that are discordant with these other data and show variable engraftment, the company said.

In addition, the company noted that in the last 12 months, multiple challenging market and regulatory dynamics for its Fabry disease program have emerged, which it said would now be exacerbated by a meaningfully extended development timeline.

 “We’re fully aware of the impact this difficult decision has on the patients and families whom we have had the privilege to get to know over the years, but we believe deprioritizing and halting enrollment in our Fabry disease program is the right step forward for Avrobio and preserves our ability to continue developing therapies with the potential to address urgent unmet needs in the lysosomal disorder community,” said McKay.

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 that 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 or serious adverse events related to drug product AVR-RD-01, as of the most recent data cut-off date.

Author: Rare Daily Staff

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