RARE Daily

FDA Lifts Hold on Astellas’ Pompe Gene Therapy

Rare Daily Staff

January 20, 2023

The U.S. Food and Drug Administration lifted the clinical hold it placed on Astellas Pharma’s FORTIS phase 1/2 clinical trial studying AT845, its experimental gene therapy for adults with late-onset Pompe disease.

Pompe disease is a rare, severe, autosomal recessive metabolic disease characterized by progressive muscular degeneration. The disease is caused by mutations in the alpha-glucosidase (GAA) gene that prevent the production and function of a protein called acid alpha-glucosidase (GAA). GAA is responsible for metabolizing glycogen, and dysfunction or absence of this protein results in the accumulation of glycogen in tissues, primarily in the skeletal and cardiac muscles, where it causes damage to tissue structure and function. Currently, the only approved treatment for Pompe is enzyme replacement therapy, which is a chronic treatment delivered in bi-weekly infusions and relies solely on tissue uptake of GAA from plasma.

Astellas is developing AT845, a novel gene replacement therapy using an AAV8 vector under a muscle-specific promotor to deliver a functional copy of the GAA gene, for the treatment of late-onset Pompe disease. AT845 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 a multicenter, open-label, ascending dose phase 1/2 first-in-human clinical trial to determine if AT845 is safe and tolerable in adults with late-onset Pompe disease. 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.

The FDA had informed Astellas that it did not have sufficient information to assess the risks to subjects and required additional information about a recently reported serious adverse event. To date, the serious adverse events have been classified by the site investigator as Grade 1 (mild in severity) and deemed serious due to medical significance. A written explanation for the basis of the hold was to be issued by the FDA and sent to Astellas within the next 30 days.

Following the clinical hold lift, Astellas said it is working on completing the clinical and regulatory activities necessary to resume dosing in the FORTIS clinical trial.

The clinical hold lift will have no impact on Astellas’ financial forecasts of the current fiscal year ending March 31, 2023.

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