- Data presented at the 18th Annual WORLDSymposiumTM 2022 -

TOKYO, Feb. 7, 2022 - Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced positive interim safety data from FORTIS, the Phase I/II clinical trial evaluating AT845, an investigational adeno-associated virus (AAV) gene replacement therapy to deliver a functional alpha-glucosidase (GAA) gene to express acid alpha-glucosidase (GAA) directly in muscle cells in adults with Late-Onset Pompe Disease (LOPD) (Presentation & Poster: 206).

Pompe disease, a rare, severe, autosomal recessive metabolic disease characterized by progressive muscular degeneration, results from a mutation in the GAA gene that interferes with the production or function of the GAA protein. GAA is responsible for metabolizing glycogen, and dysfunction or absence of this protein results in the accumulation of glycogen, primarily in the skeletal and cardiac muscles, where it causes damage to tissue structure and function. Currently, the only approved treatment for Pompe disease is enzyme replacement therapy (ERT), which is delivered via chronic intravenous infusions every two weeks and relies solely on tissue uptake of GAA from plasma.

“There is significant unmet need for patients with Pompe disease due to the short half-life, inefficient uptake in the key tissues affected by the disease and the immunogenicity of ERT,” said Tahseen Mozaffar, M.D., Professor of Neurology at UC Irvine. “AT845 has the potential to be a best-in-class approach as a muscle-directed gene therapy using an AAV8 capsid serotype. It is being investigated to determine whether it can deliver a functional GAA gene that is efficiently transduced to express GAA directly in tissues affected by the disease, including skeletal and cardiac muscle.”

FORTIS is an ongoing multicenter, open-label, ascending dose Phase I/II first-in-human clinical trial to determine if AT845 is safe and tolerable in adults with LOPD. Enrolled participants receive a one-time peripheral intravenous infusion of AT845, followed by one year of frequent monitoring of safety, clinical and biochemical endpoints including GAA activity and protein level in muscle and four additional years of long-term safety monitoring. The primary endpoints of the trial are safety and tolerability, as well as efficacy measures, including change in muscle GAA protein expression and enzyme activity from baseline. Secondary endpoints evaluate improvements in respiratory, endurance and quality of life measures.

As of the December 3, 2021 data cut-off date, four participants have been enrolled in FORTIS, with two participants dosed at 3 x 1013 vg/kg (Cohort 1) and two participants dosed at 6 x 1013 vg/kg (Cohort 2). The reported data includes interim safety and tolerability assessments, as well as up to 24 weeks of follow-up for the two participants in Cohort 1 and preliminary data from the two participants in Cohort 2. 

“We are pleased that AT845 has been well-tolerated so far in the four adults with LOPD who have received treatment,” said Weston Miller, M.D., Senior Medical Director, Clinical Development at Astellas Gene Therapies. “In the two participants in Cohort 1 with follow-up duration through week 24 after dosing, AT845 demonstrated an encouraging safety profile. Importantly, there have been no serious adverse events reported following dosing in any of the four participants as of the time of the data cut. One participant experienced elevated transaminases, which is considered a common immune-mediated treatment response based on the time of onset after dosing, its presentation during steroid taper initiation and its reversal with steroid re-initiation. These safety data are encouraging, and the program continues to enroll participants.”

With the establishment of the Astellas Gene Therapies Center of Excellence following the 2020 acquisition of Audentes Therapeutics Inc., Astellas is a leader in genetic medicines, working alongside its world-renowned partners to build a portfolio of potentially life-changing gene therapies. Astellas strives to identify, develop and deliver transformative therapies for patients with genetic diseases who currently have few or no effective treatment options. 


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