FDA puts hold on Astellas gene therapy trial, following nerve damage in patient

June 27, 2022

The FDA has placed a clinical hold on Astellas Pharma’s Pompe disease gene therapy trial after reports were made of a serious adverse event in one of the participants.

The Tokyo-based pharma company announced today that the FDA is asking for more information to thoroughly assess the risks to subjects following the occurrence of peripheral sensory neuropathy in one of the trial participants. The trial, FORTIS, is a phase 1/2 trial that is investigating Astella’s AT845 gene therapy in adults with late-onset Pompe disease (LOPD).

Usually diagnosed at birth, Pompe disease is a rare, severe, metabolic disease characterized by muscular degeneration. The disease is a result of mutations in the alpha-glucosidase gene (GAA), which is responsible for the production and function of a protein by the same name. Because GAA plays a crucial role in how the body metabolizes glycogen or sugars, dysfunction in this protein causes a glycogen buildup in tissue, such as cardiac or skeletal muscles.

Astellas’ AT845 is a gene replacement therapy that uses an adeno-associated virus AAV8 vector to deliver a functional copy of the GAA gene to treat LOPD. Currently, there is only one enzyme replacement therapy treatment approved for Pompe — Sanofi's Nexviazyme.

Following the clinical hold, Astellas will have to work with the FDA to review all relevant data before enrolling new patients in the trial. The adverse reaction reported was classified by the site investigator as Grade 1, or mild in severity. 

In 2021, Astellas voluntarily paused screening and dosing in a different gene therapy clinical trial due to safety issues. Earlier that year the company reported an impairment loss of about $540 million due to another FDA clinical hold.