AVROBIO Provides Regulatory Update on Investigational AVR-RD-01 for Fabry Disease

CAMBRIDGE, Mass. – AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today provided an update on its regulatory plans for AVR-RD-01, the first investigational lentiviral gene therapy for Fabry disease. This update follows a recent U.S. regulatory development for Fabry disease therapies, as well as AVROBIO’s receipt of minutes from the company’s Type B (End-of-Phase 1) meeting with the U.S. Food and Drug Administration (FDA) on March 31, 2021.

On March 11, 2021, approximately three weeks before the company’s End-of-Phase 1 meeting, FDA granted full approval of Fabrazyme® (agalsidase beta)1 more than 18 years after the enzyme replacement therapy (ERT) received accelerated approval on the basis of a surrogate endpoint: reduction of GL-3 (also referred to as Gb3) inclusions in biopsied renal peritubular capillaries (PTCs). The conversion of Fabrazyme to full approval opens a new pathway for full approval of ERTs based on this surrogate endpoint, which AVROBIO believes could potentially apply to investigational AVR-RD-01. In addition, the conversion of Fabrazyme to full approval limits the accelerated approval pathways available for new therapies to treat Fabry disease. As a result, AVROBIO can no longer pursue an accelerated approval pathway for AVR-RD-01 with the FAB-GT trial as currently designed, and instead intends to discuss with FDA a registration trial with a primary efficacy endpoint of clearance of GL-3/Gb3 inclusions in biopsied renal PTCs as the basis for full approval.

“We believe we have a potential new path to pursue full approval for investigational AVR-RD-01 as a first-line therapy for Fabry disease by conducting a single, head-to-head registration trial versus Fabrazyme using a kidney biopsy surrogate endpoint similar to our FAB-GT Phase 2 trial, where we have seen 100% and 87% substrate reductions at one year post-gene therapy in the two patients with evaluable kidney biopsies,” said Geoff MacKay, CEO and president of AVROBIO. “We plan to design a registration trial with a scope, size and duration comparable to other gene therapy trials.”

In its FDA briefing book, which was submitted to FDA prior to Fabrazyme’s full approval, the company sought an accelerated approval pathway by expanding the FAB-GT Phase 2 clinical trial and conducting an additional confirmatory trial. The revised regulatory plan anticipates retaining the two-study approach with a similar overall requirement in terms of scope, size and duration.

The company plans to engage FDA to discuss and agree upon its revised approach, with the goal of initiating the registration trial in mid-2022. Although FDA guidance provides that a surrogate endpoint in a particular clinical development program should not be assumed to be appropriate for use in a different program, AVROBIO believes this recent development could potentially apply to investigational AVR-RD-01, a gene therapy designed to facilitate the production of functional enzyme by the patient’s own stem cells after a one-time treatment with the therapeutic gene.

AVROBIO also remains on track to request a CMC-oriented Type C meeting in the second half of 2021. Additionally, in parallel the company intends to seek scientific advice from the European Medicines Agency on the planned registration trial.

Two additional patients dosed in two months, with plans to amend the FAB-GT trial protocol

The ongoing FAB-GT trial continues to progress, now with six patients dosed, including two in the past two months, and additional participants are enrolled in the trial.

To help support the use of AVR-RD-01 in a broad Fabry disease population, AVROBIO expects to amend the FAB-GT trial protocol in the second quarter of 2021 by enrolling female participants, eliminating antibody-status exclusions and adding the collection of data on additional parameters that are recognized to be limitations of ERT, such as endpoints to assess the gene therapy’s potential ability to address cardiovascular and central nervous system manifestations. The company plans to enroll a total of up to 14 participants in the FAB-GT trial.

“We look forward to working with FDA and other regulators to design a single registration trial to support full approval that we hope will advance AVR-RD-01 as quickly as possible. We remain fiercely committed to our purpose: to free people living with Fabry disease from a lifetime of painful symptoms, chronic treatment and the unremitting fear of disease progression,” added MacKay.

About AVR-RD-01

AVR-RD-01 is an investigational ex vivo lentiviral gene therapy designed to provide a durable therapeutic benefit for people living with Fabry disease. The therapy starts with the patient’s own hematopoietic stem cells, which are genetically modified to express functional alpha-galactosidase A (AGA). Functional AGA reduces levels of globotriaosylceramide (Gb3 or GL-3), a toxic substrate, which together with its metabolite globotriaosylsphingosine (lyso-Gb3 or lyso-GL1), are associated with the signs and symptoms of Fabry disease. AVR-RD-01 has received orphan drug designations from FDA and the European Commission. AVROBIO is currently evaluating AVR-RD-01 in FAB-GT (NCT03454893), a Phase 2 clinical trial.

About Fabry Disease

Fabry disease is a rare, inherited lysosomal disorder characterized by the accumulation of globotriaosylceramide (Gb3 or GL-3) in the body’s cells. The build-up of Gb3 is due to variations in the GLA gene, which is responsible for the production of alpha-galactosidase A, the enzyme that breaks down Gb3. When Gb3 accumulates in cells and tissues, damage may occur and result in the progressive signs and symptoms of Fabry disease, including chronic pain, gastrointestinal issues such as nausea, vomiting and diarrhea, hearing loss, heart disease, progressive kidney disease and an increased risk of stroke. Even on ERT – the current standard of care – people with Fabry disease typically have a shortened life expectancy and may experience debilitating symptoms that significantly reduce their quality of life. An estimated one in 40,000 to 60,000 males are diagnosed with Fabry disease. Fabry disease also affects females, although the prevalence is unknown.


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.


Christopher F. Brinzey
Westwicke, an ICR Company
[email protected]

Stephanie Simon
Ten Bridge Communications
[email protected]