AVROBIO Presents Clinician Experience with FAB-GT Clinical Trial and Updated Safety Data for Investigational Gene Therapies in Fabry Disease and Gaucher Disease Type 1
Safety data updates for Phase 1 and 2 Fabry disease clinical trials and Phase 1/2 Gaucher disease type 1 clinical trial show no adverse events or serious adverse events related to drug product
During the panel discussion, the clinicians discussed the patient experience during apheresis (the process by which the patient’s stem cells are collected), conditioning (the process to clear space in the patient’s bone marrow to receive their stem cells back following introduction of the therapeutic transgene), and infusion of the genetically modified stem cells, as well as after receiving the gene therapy.
“It’s been exciting and rewarding to be part of this first-in-the-world clinical trial to bring this investigational gene therapy to the Fabry disease community here in Australia,” said
Nine patients have been dosed in the FAB-GT clinical trial to date, all of them in
“From our perspective, every patient has a different story, so personalization is the best approach when discussing and providing treatment,” added
“Based on the patients with various lysosomal disorders I have treated, I believe lentiviral gene therapy has the potential to be transformative because it can deliver more enzyme to the brain, to soft tissues, like the heart, lungs and liver, as well as into the skeleton,” commented
Updated safety data show no adverse events or serious adverse events related to drug product
Phase 1 and Phase 2 studies for Fabry disease
- Safety data from the first eight adult patients dosed in the Phase 2 FAB-GT trial (mean, range post-gene therapy follow-up: 16, 5-41 months) and the five adult patients dosed in the investigator-sponsored Phase 1 trial (mean, range post-gene therapy follow-up: 39, 33-58 months) show no adverse events (AEs) or serious adverse events (SAEs) related to drug product AVR-RD-01.
- AEs and SAEs experienced by trial participants to date have been generally consistent with myeloablative conditioning, protocol-mandated drugs, underlying disease or pre-existing conditions. Eleven SAEs (nausea, vomiting, dehydration, fever, febrile neutropenia and mucosal inflammation) were reported; all resolved without clinical sequelae.
- Safety data from a ninth patient recently dosed in the FAB-GT study are still being analyzed, but preliminary data are consistent with the overall safety profile.
- Previously reported efficacy data from the two trials have documented stable and sustained enzyme activity and reductions of 87% and 100% in kidney Gb3 inclusions for the evaluable kidney biopsies of two Fabry disease patients.
AVROBIOis planning to share updated efficacy data from both trials during the first quarter of 2022.
- The safety data cut-off date for the Phase 1 trial was
July 26, 2021, and for the FAB-GT trial was Aug. 20, 2021. Enrollment in the FAB-GT trial (NCT03454893) is ongoing, and further details are available on clinicaltrials.gov.
The Guard1 study for Gaucher disease type 1
- Safety data from the first patient dosed in the first in-human, open-label, multinational Phase 1/2 study of AVR-RD-02 (treated using AVROBIO’s proprietary plato® gene therapy platform) show no SAEs and no AEs to date related to drug product 14 months post-treatment.
- AEs reported for this patient have been consistent with myeloablative conditioning, protocol-mandated drugs, underlying disease and pre-existing conditions.
- This patient discontinued ERT one month before the gene therapy infusion and remains off ERT. Previously reported efficacy data for this patient indicates improvement across relevant biomarkers of Gaucher disease type 1. Platelet and hemoglobin concentration levels were maintained in the normal range.
- A second patient has been dosed in the clinical trial.
- The safety data cut-off date for the Phase 1 trial was
Aug. 31, 2021. Enrollment in the Guard1 trial (NCT04145037) is ongoing, and further details are available on clinicaltrials.gov.
Preclinical data for Hunter syndrome
- Current clinical treatments for Hunter syndrome include ERT and hematopoietic stem cell (HSC) transplant, but neither is efficacious at treating neurological symptoms due to deficiencies in enzyme expression.
- Published preclinical research by the team at
The University of Manchesterin mice has demonstrated that lentiviral gene therapy with an optimized, proprietary tag can cross the blood-brain barrier and has the potential to deliver the functional enzyme (iduronate 2-sulfatase, or I2S) to the CNS.
- Preclinical evidence shows that, compared to untreated Hunter mice, Hunter mice treated with genetically modified HSCs at 10-12 months post-gene therapy have supra-physiological levels of I2S enzyme activity in the bone marrow, plasma and spleen (among other tissues and organs) and increased I2S enzyme activity levels in the brain, with no unexpected safety events to date.
AVROBIOplans to initiate an investigator-sponsored Phase 1/2 clinical trial of AVR-RD-05 in Hunter syndrome in the second half of 2022. AVROBIOannounced an exclusive, worldwide license agreement with The University of Manchesterfor this investigational lentiviral gene therapy in 2020.
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. Our ex vivo lentiviral gene therapy pipeline includes clinical programs in Fabry disease, Gaucher disease type 1 and cystinosis, as well as preclinical programs in Hunter syndrome, Gaucher disease type 3 and Pompe disease.
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 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, the timing of patient recruitment and enrollment activities, and product approvals, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, and the expected benefits and results of our implementation of the plato® platform in our clinical trials and gene therapy programs, including the use of a personalized and ultra-precision busulfan conditioning regimen. 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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