GAINESVILLE, Fla. and CAMBRIDGE, Mass. and PHILADELPHIA, Jan. 20, 2016 (GLOBE NEWSWIRE) -- Applied Genetic Technologies Corporation (Nasdaq:AGTC), a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare diseases, today announced data evaluating the use of recombinant AAV-AAT vector gene delivery to muscle in patients with alpha-1-antitrypsin (AAT) deficiency, an inherited genetic disorder that results in severe loss of lung function and is caused by complete or partial deficiency of the alpha-1 antitrypsin protein. Results were published online in the peer-reviewed journal Human Gene Therapy and will appear in the January print issue of the journal.
“Currently, individuals affected by pulmonary manifestations of AAT deficiency are frequently treated with weekly intravenous infusions of AAT derived from donated human plasma, a procedure that is inconvenient and cost prohibitive,” said Philip R. Johnson, M.D., corresponding study author. “Phase 2 human studies evaluating gene transfer as a potential treatment option have been encouraging and these data further suggest that a one-time, AAV-based intramuscular AAT vector injection can have a durable response and direct sustained expression of the AAT protein.”
In this study, 3 cohorts of 3 subjects each had received rAAV1-AAT by intramuscular injection at doses of 6 × 1011 (low), 1.9 × 1012 (mid), or 6 × 1012 (high) vector genomes per kilogram of body weight. Muscle biopsies at the injection site were performed at 3 months after vector injection in all 9 subjects and at 12 months after vector injection in 8 of the 9 subjects enrolled in the trial. Samples of DNA obtained from these biopsies were characterized in depth by investigators at the Children’s Hospital of Philadelphia.
Each biopsy sample contained readily detectable vector DNA, the majority of which was in the form of double-stranded supercoiled and open circular episomes (segments of DNA separate from the chromosome). Episomes persisted in all participants through 12 months at only slightly lower levels than those observed at 3 months. The highest copy numbers were found in a subject in the high-dose cohort, and serum AAT levels at 12 months confirmed that the high-dose group also had the highest sustained serum AAT levels. Molecular clones of vector genomes derived directly from the biopsies were transcriptionally active, potentially identifying them as the source of serum AAT in the trial subjects.
“These results suggest that AAV vectors made using AGTC’s proprietary manufacturing method are able to achieve sustained expression of the AAT protein for at least one year after one-time treatment, and we will continue to monitor patients to better understand the durability of expression over a longer time period,” said Sue Washer, CEO of AGTC. “The study outcomes support our ongoing efforts to develop AAV vector products for a range of therapeutic indications.”
About AGTC
AGTC is a clinical-stage biotechnology company that uses its proprietary gene therapy platform to develop products designed to transform the lives of patients with severe diseases, with an initial focus in ophthalmology. AGTC's lead product candidates focus on inherited orphan diseases of the eye, caused by mutations in single genes that significantly affect visual function and currently lack effective medical treatments.
AGTC’s product pipeline includes six named ophthalmology development programs across five targets (X-linked retinoschisis (XLRS), X-linked retinitis pigmentosa (XLRP), achromatopsia, wet age-related macular degeneration and blue cone monochromacy), one non-ophthalmology program (alpha-1 antitrypsin deficiency) and proof-of-concept data in multiple additional indications. AGTC employs a highly targeted approach to selecting and designing its product candidates, choosing to develop therapies for indications having high unmet medical need, clinical feasibility and commercial potential. AGTC has a significant intellectual property portfolio and expertise in the design of gene therapy products including capsids, promoters and expression cassettes, as well as, expertise in the formulation, manufacture and physical delivery of gene therapy products.
Forward Looking Statements
This release contains forward-looking statements that reflect AGTC's plans, estimates, assumptions and beliefs. These statements relate to a variety of matters, including but not limited to, the anticipated utility of AAV vectors made using AGTC’s proprietary manufacturing method in the treatment of AAT deficiency and other therapeutic indications. Forward-looking statements include all statements that are not historical facts and can be identified by terms such as "anticipates," "believes," "could," "seeks," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," "would" or similar expressions and the negatives of those terms. Actual results could differ materially from those discussed in the forward-looking statements, due to a number of important factors, which include, but are not limited to, the following: no gene therapy products have been approved in the United States and AGTC cannot predict when or if it will obtain regulatory approval to commercialize a product candidate; AGTC relies on third parties to conduct, supervise and monitor its clinical trials and to conduct certain aspects of its product manufacturing and protocol development; and increased regulatory scrutiny of gene therapy and genetic research could damage public perception of AGTC’s product candidates or adversely affect AGTC’s ability to conduct its business. Additional factors that could cause actual results to differ materially from those described in the forward-looking statements are set forth under the heading “Item 1A—Risk Factors" in AGTC's Annual Report on Form 10-K for the fiscal year ended June 30, 2015, as filed with the SEC. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Also, forward-looking statements represent management's plans, estimates, assumptions and beliefs only as of the date of this release. Except as required by law, AGTC assumes no obligation to update these forward-looking statements publicly or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.