CAMBRIDGE - AVROBIO, Inc. (Nasdaq: AVRO) (the 'Company'), a Phase 2 clinical-stage gene therapy company, today announced clinical trial updates from the ongoing investigator-sponsored Phase 1 clinical study and the AVROBIO-sponsored Phase 2 clinical trial of AVR-RD-01.
AVR-RD-01 is an investigational gene therapy candidate designed to treat Fabry disease by inserting the GLA gene that encodes functional -galactosidase A (AGA, the enzyme that is deficient in patients with Fabry disease) with the goal of enabling continuous endogenous AGA production and distribution to tissues and organs.
AVROBIO WORLD Fabry Chart 1 - Phase 1 AGA enzyme activity (Graphic: Business Wire)
'Today's update shows a consistent readout across multiple surrogate markers that support the potential of AVR-RD-01 to address the genetic basis of Fabry disease,' said Birgitte Volck, MD, PhD, AVROBIO's President of Research and Development. We believe these results are significant because the data reported show sustained AGA enzyme levels with associated reductions in substrate and metabolite levels. This suggests that our gene therapy exerts its effects as intended in patients previously treated with ERT, as well as in treatment-naive patients. Taken together, these clinical data represent a growing body of evidence of the therapeutic potential of AVR-RD-01 as a gene therapy for patients with Fabry disease.'
The investigator-sponsored Phase 1 study is designed to assess the safety of AVR-RD-01 in up to six patients with Fabry disease who have been treated with standard of care enzyme replacement therapy (ERT) for at least six months prior to receiving AVR-RD-01. The AVROBIO-sponsored Phase 2 trial of AVR-RD-01 (the FAB-201 Study1) is an open-label, single-arm clinical trial evaluating the efficacy and safety of AVR-RD-01 in eight to twelve treatment-naive patients who have not received ERT.
To date, six patients have been dosed in the AVR-RD-01 studies - four patients in the Phase 1 study and two patients in the Phase 2 study. Across both studies, four patients have reached the point of three-month data analysis or longer after receiving AVR-RD-01 - three patients in the Phase 1 study and one patient in the Phase 2 study. Clinical data for these four patients are detailed in this update.
About Fabry Disease
Fabry disease is a rare lysosomal storage disease associated with significant morbidity and early mortality. It is caused by a gene defect that causes a deficiency in functional enzyme -galactosidase A (AGA), which breaks down a particular type of fat in the body's cells known as globotriaosylceramide, or Gb3. As Gb3 and other related substrates increase in patients with Fabry disease, Gb3 and its metabolites (principally lyso-Gb3) becomes toxic to the patient's cells. Gb3 and other glycosphingolipids accumulate and result in damage to multiple tissues and organs, especially the kidneys, heart and brain. Accumulation of Gb3 in tissues such as the heart and the vascular system can lead to life threatening vascular blockages and thus to stroke and heart attacks. In addition, high levels of Gb3 substrate accumulation in the kidney can cause kidney failure. Gb3 can also accumulate in other tissues, such as the nervous system, where it leads to debilitating pain. Due to end-stage renal disease and other life-threatening complications associated with Fabry disease, the average life expectancy in affected males is approximately 58 years of age. Most patients with Fabry disease begin experiencing chronic pain in childhood but are often not diagnosed with Fabry disease until their twenties, due to a broad variation in patient symptoms. Over 1,000 gene mutations associated with Fabry disease have been identified. It is estimated that Fabry disease is diagnosed in approximately one in 40,000 males and one in 118,000 females in the United States, but studies have suggested that a larger number of patients may be undiagnosed.
AVR-RD-01 is an ex vivo lentiviral gene therapy being investigated as a single-dose therapy with the potential to provide durable and life-long potential therapeutic benefit for patients with Fabry disease. AVR-RD-01 is designed to employ a state-of-the-art lentiviral vector system that is an efficient gene transfer technology for the permanent integration of functional copies of the gene into the patient's own stem cells. In patients with Fabry disease, hematopoietic stem cells are collected from the patient, and then transduced with lentiviral vector carrying a functional version of the GLA gene that encodes active -galactosidase A (AGA) - the enzyme that is deficient in Fabry disease - to create AVR-RD-01 gene therapy. AVR-RD-01 is then infused back into the patient with the goal of restoring normal GLA gene expression such that functional AGA enzyme is sufficiently produced by the patient's own body.
About AVROBIO, Inc.
AVROBIO, Inc., is a Phase 2 clinical-stage gene therapy company developing gene therapies to potentially cure rare diseases with a single dose. AVROBIO's lentiviral-based gene therapies employ hematopoietic stem cells that are collected from the patient and then modified with a lentiviral vector to insert functional copies of the gene that is defective in the target disease. AVROBIO is focused on the development of its gene therapy, AVR-RD-01, in Fabry disease, as well as additional gene therapy programs in other lysosomal storage disorders including Gaucher disease, cystinosis and Pompe disease. The Company's plato platform is a vector system and automated, closed, cell manufacturing solution designed to support worldwide commercialization. AVROBIO is headquartered in Cambridge, MA and has offices in Toronto, ON.
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 such as 'aims,' 'anticipates,' 'believes,' 'could,' 'estimates,' 'expects,' 'forecasts,' 'goal,' 'intends,' 'may,' 'plans,' 'possible,' 'potential,' 'seeks,' 'will,' and variations of these words or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy, prospective products and goals, the therapeutic potential of our product candidates, the design, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, potential regulatory approvals and the timing thereof, anticipated benefits of our gene therapy platform, timing and likelihood of success, plans and objectives of management for future operations, future results of anticipated products, and the market opportunity for our product candidates. 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 realize the intended benefits of our gene therapy 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, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates.
Christopher F. Brinzey