AVROBIO Reprioritizes Pipeline Programs
AVROBIO Reprioritizes Pipeline Programs
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
"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
“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
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 Manchesterplan 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
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
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our plans and expectations for reprioritizing our program pipeline, including the deprioritization of our Fabry disease clinical program, our business strategy for and the potential therapeutic benefits of our prospective product candidates, results of preclinical studies, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, anticipated regulatory interactions, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato® platform in our clinical trials and gene therapy programs, the potential use of monoclonal antibody conditioning agents, and our financial position and cash runway expectations. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.
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i Collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 is funded in part by grants to