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

AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a vision to free people from a lifetime of genetic disease, today hosted a panel of investigators managing the patient experience in the Phase 2 FAB-GT clinical trial of AVR-RD-01, an investigational one-time gene therapy for Fabry disease, at the 14th International Congress of Inborn Errors of Metabolism (ICIEM), Nov. 21-23, 2021, in Sydney, Australia. Other presentations included updated safety data from the first lentiviral gene therapy clinical trials for Fabry disease and Gaucher disease type 1, as well as 10- to 12-month safety data from gene therapy-treated mice with mucopolysaccharidosis type II (MPSII), or Hunter syndrome.

Chaired by Rob Wynn, M.D., (consultant pediatric hematologist at the Royal Manchester Children’s Hospital, UK), the AVROBIO sponsored symposium, Advancing the patient experience during ex vivo lentiviral gene therapy for lysosomal disorders, featured trial investigators Mark Thomas, M.D., (Royal Perth Hospital, WA, AUS; clinical professor at the University of Western Australia Medical School), Kathy Nicholls, M.D., (Royal Melbourne Hospital, VIC, AUS) and Ben Carnley, M.D., (Royal Perth Hospital, WA, AUS), who discussed managing the patient experience with ex vivo lentiviral gene therapy based on their involvement in the FAB-GT clinical trial.

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 Dr. Nicholls. “While the current standard of care has made an important difference in the lives of patients, there are limitations in the impact of enzyme replacement therapy (ERT) on the heart, kidney and central nervous system (CNS) manifestations of Fabry disease. For instance, we know that renal progression will continue even on a combination of ERT and other renal protective measures. We’d like this not to be the case, of course. We need better treatment options for these patients and families.”

Nine patients have been dosed in the FAB-GT clinical trial to date, all of them in Australia. While the first three patients were treated using an academic vector and melphalan as a conditioning agent, the other six patients were treated using AVROBIO’s proprietary plato® gene therapy platform, which includes a state-of-the-art lentiviral vector, a personalized busulfan conditioning regimen designed to implement precision dosing and an automated, closed manufacturing process intended to deliver potent and consistent drug product from manufacturing sites worldwide at commercial scale.

“From our perspective, every patient has a different story, so personalization is the best approach when discussing and providing treatment,” added Dr. Thomas. “Making sure that you explain every step of the process – preferably several times and in sections to give patients and families time to fully understand the information – has been an important part of preparing patients for gene therapy. Comprehensive patient support, provided by a dedicated care team, sets clear expectations and can help improve the overall patient experience.”

“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 Prof. Wynn, who is not an investigator in the FAB-GT trial. “This trial discussed today and others like it help pave the way for ex-vivo lentiviral gene therapy approaches for lysosomal disorders. I encourage everyone to come with us as we embark and continue on this journey of changing from ERT, allogeneic transplant therapy and supportive care to ex-vivo lentiviral gene therapy approach using a patient’s own genetically modified hematopoietic stem cells.”

Updated safety data show no adverse events or serious adverse events related to drug product

AVROBIO also presented updated clinical and preclinical data from the company’s pipeline of lysosomal disorder programs in one oral and two poster presentations.

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. AVROBIO is 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 Manchester in 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.
  • AVROBIO plans to initiate an investigator-sponsored Phase 1/2 clinical trial of AVR-RD-05 in Hunter syndrome in the second half of 2022. AVROBIO announced an exclusive, worldwide license agreement with The University of Manchester for 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. AVROBIO is powered by our industry-leading plato® gene therapy platform, our foundation designed to deliver gene therapy worldwide. 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.

Forward-Looking Statement

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.

Any forward-looking statements in this press release are based on AVROBIO’s current expectations, estimates and projections about our industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIO’s product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato® platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIO’s product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO’s actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled “Risk Factors” in AVROBIO’s most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO’s subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.


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