Fabry disease program to be deprioritized, shifting focus to other clinical-stage programs in lysosomal disorder pipeline

Data updates for cystinosis and Gaucher disease type 1 programs planned for 1H 2022, with regulatory interactions anticipated across multiple programs in 2022

Cash runway to be extended into first quarter of 2024

CAMBRIDGE, MA, USA I January 04, 2021 IAVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a shared purpose to free people from a lifetime of genetic disease, today 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.

“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.

“Previously reported data from 13 patients treated across our 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. In addition, the last 12 months have presented multiple challenging market and regulatory dynamics for our Fabry disease program, which would now be exacerbated by a meaningfully extended development timeline,” said MacKay. “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.”

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. (See data slides here)

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.

“Importantly, the drug product specifications for these five patients met all release criteria,” said MacKay. “Additionally, these variable engraftment patterns have not been observed to date in data from the other nine Fabry disease patients previously dosed in the Phase 1 trial and under the prior protocol amendments in the FAB-GT trial, or in data from any patients in our other ongoing clinical trials.”

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.

Updated 2022 program guidance
Anticipated pipeline milestones include:

  • AVR-RD-04 for cystinosis: Provide an update at the WORLDSymposium™ 2022 on collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 (CTNS-RD-04),i and plan to engage with regulatory agencies on a planned Phase 2 company-sponsored clinical trial
  • AVROBIO’s Gaucher disease programs:
    • AVR-RD-02 for Gaucher disease type 1: Provide a clinical update in the first half of 2022
    • AVR-RD-06 for Gaucher disease type 3: Engage with regulatory agencies on a planned Phase 2/3 clinical development strategy for AVR-RD-06; planning to initiate a clinical trial in 2023
  • AVR-RD-05 for Hunter syndrome: Collaborators at the University of Manchester plan to initiate a collaborator-sponsored Phase 1/2 clinical trial in 2023
  • AVR-RD-03 for Pompe disease: Engage with regulatory agencies on the clinical development strategy for AVR-RD-03; planning to initiate a clinical trial in 2023
  • plato® platform: Continue research collaborations to evaluate the potential use of monoclonal antibody conditioning agents in Gaucher disease type 1 trial

As of Sept. 30, 2021, the company had $201 million in cash and cash equivalents. As a result of the pipeline reprioritization, the company expects to extend its cash runway into the first quarter of 2024.

Our vision is to bring personalized gene therapy to the world. We aim to prevent, halt or reverse disease throughout the body with a single dose of gene therapy designed to drive durable expression of therapeutic protein, even in hard-to-reach tissues and organs including brain, muscle and bone. AVROBIO’s pipeline is powered by our industry-leading plato® gene therapy platform, our foundation designed to deliver gene therapy worldwide. It includes clinical programs in cystinosis and Gaucher disease type 1, as well as preclinical programs in Gaucher disease type 3, Hunter syndrome and Pompe disease. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

i Collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 is funded in part by grants to UCSD from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH).

SOURCE: Avrobio