Astellas' gene therapy strategy faces fresh setback as FDA puts Pompe disease med on hold

Astellas’ gene therapy ambitions have faced yet another setback. The FDA has slammed the brakes on a phase 1/2 study of the Japanese pharma’s Pompe disease med while the regulator investigates a report of nerve damage in one of the trial’s participants.

The gene replacement therapy, dubbed AT845, is being investigated in the FORTIS trial of 12 individuals with late-onset Pompe disease, who each receive one infusion of the adeno-associated virus gene therapy. The trial began in October 2020 with an estimated primary completion date of December 2022, according to

This timeline may be sent off course by the news that one of these participants has suffered a serious adverse event (SAE) of peripheral sensory neuropathy, a result of damage to the nerves located outside of the brain and spinal cord, leading to a clinical hold from the FDA.

“The FDA informed Astellas that it did not have sufficient information to assess the risks to subjects and requires additional information about the recently reported SAE,” the Japanese pharma said in a June 27 announcement.

The SAE has been classified by the site investigator as grade 1, indicating it is mild in severity, but it was deemed serious due to medical significance, Astellas said. The regulator will provide a written explanation for the basis of the hold to the company within the next 30 days.

Astellas is working with the site investigator to closely follow the patient's clinical course and will continue to gather and review all relevant data, the company said. The other enrolled participants will continue to be monitored closely per the study protocol, it added.

"Patient safety is our top priority, and we are working closely with the FDA to determine appropriate next steps," said Weston Miller, M.D., senior medical director of 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 with updates as we learn more."

Pompe disease is a rare, severe, autosomal recessive metabolic disease characterized by progressive muscular degeneration. The only approved treatment for the condition is enzyme replacement therapy, which is delivered in biweekly infusions.

AT845 is not the only gene therapy from Astellas that has run into trouble in the past year. A trial of AT132—which like AT845 was acquired in the $3 billion buyout of Audentes—for a rare neuromuscular disease has been halted by the FDA on two separate occasions over a total of four patient deaths to date.

Astellas also scrapped three other gene therapy assets from the Audentes deal, all targeting Duchenne muscular dystrophy (DMD), in April after reviewing data. The DMD termination resulted in a reported $170 million impairment loss by the company, adding to the $540 million lost by the pause on AT132.

In today’s announcement, Astellas said it is reviewing the potential financial impacts of the latest clinical hold.