TOKYO, June 26, 2022 /PRNewswire/ — Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) announced that the United States Food and Drug Administration (FDA) has suspended the Phase 1/2 clinical trial of FORTIS following the occurrence of a serious adverse event (SAE ) peripheral sensory neuropathy in one of the trial participants. FORTIS is a clinical trial evaluating AT845, an investigational adeno-associated virus (AAV) gene replacement therapy in adults with late-onset Pompe disease.

The FDA has informed Astellas that it does not have sufficient information to assess risk to subjects and requires additional information on the recently reported SAE. To date, the SAE has been classified by the site investigator as Grade 1 (mild in severity) and deemed serious due to its medical significance. A written explanation of the basis for the suspension will be issued by the FDA and sent to Astellas within the next 30 days.

Astellas is working with the site investigator to closely monitor the patient’s clinical progress and will continue to gather and review all relevant data. All currently enrolled participants will continue to be closely monitored in accordance with the study protocol.

“Patient safety is our top priority, and we are working closely with the FDA to determine appropriate next steps,” explained Weston Miller, MD, Senior Medical Director, Clinical Development at Astellas Gene Therapies. “We remain committed to the safe and effective development of AT845 and will keep the scientific and patient communities informed of updates as we learn more.”

Astellas is focused on the development of genetic drugs and works alongside its world-leading partners to build a portfolio of potentially life-changing gene therapies. Astellas strives to identify, develop and deliver therapies to patients with genetic diseases who currently have few or no effective treatment options.

Astellas is reviewing the potential financial impacts of this case for the fiscal year ending March 31, 2023.

About Pompe disease
Pompe disease is a rare, severe, autosomal recessive metabolic disease characterized by progressive muscle degeneration. The overall incidence is estimated at around 1 in 40,000 births¹although the frequency and progression of the disease varies with age of onset, ethnicity, and geography.² The disease is caused by mutations in alpha-glucosidase (GAA) gene that prevents the production and function of a protein called acid alpha-glucosidase (GAA). GAA is responsible for glycogen metabolism, and dysfunction or absence of this protein results in the accumulation of glycogen in tissues, primarily in skeletal and cardiac muscles, where it damages tissue structure and function. Currently, the only approved treatment for Pompe is enzyme replacement therapy (ERT), which is a chronic treatment given as twice-weekly infusions and relies solely on tissue uptake of GAA from plasma.

About AT845 for the treatment of late-onset Pompe disease (LOPD)
Astellas is developing AT845, a novel gene replacement therapy using an AAV8 vector under a muscle-specific promoter to deliver a functional copy of the GAA gene, for the treatment of LOPD. AT845 is being investigated to determine if it can provide a GAA gene that is efficiently transduced to express GAA directly in disease-affected tissues, including skeletal and cardiac muscle.

About FORTIS
FORTIS (NCT04174105) is a first-in-man, multicenter, open-label, dose-escalating Phase I/II clinical trial to determine whether AT845 is safe and tolerable in adults with LOPD. The primary endpoints of the trial are safety and tolerability, as well as measures of efficacy, including change in muscle GAA protein expression and enzyme activity from baseline. Secondary endpoints assess improvements in respiratory, endurance, and quality of life measures.

About Astellas
Astellas Pharma Inc. is a pharmaceutical company with operations in more than 70 countries around the world. We promote the focus area approach which is designed to identify opportunities for the continued creation of new medicines to treat diseases with high unmet medical need by focusing on biology and modality. Additionally, we also look beyond our core focus of Rx to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different areas from external partners. Through these efforts, Astellas is at the forefront of change in healthcare to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

About Astellas Gene Therapies
Astellas Gene Therapies is an Astellas Center of Excellence that develops genetic medicines that have the potential to bring transformative value to patients. Based on an innovative scientific approach and industry-leading in-house manufacturing capability and expertise, we are currently exploring three gene therapy modalities: gene replacement, exon skipping gene therapy and vectored RNA knockdown and we will also advance other Astellas gene therapy programs to clinical investigation. We are based at San Franciscowith manufacturing and laboratory facilities at South of San Francisco and Sanford, North Carolina

Cautionary Notes
In this press release, statements made regarding current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management’s current assumptions and beliefs in light of information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. These factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations relating to pharmaceutical markets, (ii) exchange rate fluctuations, (iii) delays in the launch of new products, (iv) Astellas’ inability to effectively market existing and new products, (v) Astellas’ inability to continue to effectively research and develop customer-accepted products in highly competitive markets, and (vi) violations of Astellas’ intellectual property rights by third parties.

Information about pharmaceutical products (including products under development) that is included in this press release is not intended to constitute advertising or medical advice.

References
¹Kishnani, PS, et al. Guide to the diagnosis and management of Pompe disease. Genetics in Medicine: Official Journal of the American College of Medical Genetics, 2006. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110959/

²Ausems MG, et al. Frequency of type II glycogen storage disease in The Netherlands: implications for genetic diagnosis and counselling. European Journal of Human Genetics, 1999. Available from: https://www.nature.com/articles/5200367.pdf?origin=ppub; Lin CY, et al. Pompe disease in the Chinese and prenatal diagnosis by assay of alpha-glucosidase activity. Journal of Inherited Metabolic Disease, 1987. Available from: https://pubmed.ncbi.nlm.nih.gov/3106710/; Hirschhorn R, et al. Pediatric Research, 2004; Bashan N, et al. Type II glycogen storage disease in Israel. Israel Journal of Medical Sciences, 1988. Available from: https://europepmc.org/article/med/3132435; Meikle PJ, et al. Prevalence of lysosomal storage disorders. JAMA, 1999. Available from: https://jamanetwork.com/journals/jama/article-abstract/188380

SOURCEAstellas Pharma Inc.