Clinical Trial Testing Pompe Disease Gene Therapy Put on Hold

Avatar photoÖzge Özkaya, MSc, PhD
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A phase 1/2 clinical trial evaluating the safety and efficacy of an experimental gene therapy for Pompe disease was put on clinical hold by the US Food and Drug Administration (FDA) following a serious adverse event of peripheral sensory neuropathy in 1 patient during the trial.

“Patient safety is our top priority,” Weston Miller, MD, the senior medical director of clinical development at Astellas Gene Therapies, the developers of the gene therapy, said in a press release. “We are working closely with the FDA to determine appropriate next steps.”

The experimental therapy, called AT845, uses an adeno-associated virus serotype 8 (AAV8) vector to deliver a healthy copy of the GAA gene, which is mutated in Pompe disease, under a muscle-specific promoter.

The trial, named FORTIS, is an open-label, ascending-dose, multicenter study evaluating AT845 in an estimated 12 participants with late-onset Pompe disease, aged 18 and over, who can or cannot walk.

Read more about gene therapy and other experimental therapies for Pompe disease

Patients receive 1 of 3 doses of AT845 via intravenous infusion. The primary outcome measures are safety, tolerability, and GAA protein expression and enzymatic activity. Secondary outcome measures include improvements in respiratory, endurance, and quality of life measures.

The peripheral sensory neuropathy observed during the trial was classified as mild in severity but deemed serious because of its medical significance. The patient’s clinical course will be closely followed and the other participants will continue to be monitored closely, according to the company.

The trial started on October 28, 2020, and was estimated to be completed in January 2027. Dr. Miller said the developers “remain committed to the safe and effective development of AT845 and will keep the scientific and patient communities informed with updates as [they] learn more.”

References

Astellas announces FDA update on the FORTIS clinical trial of AT845 in adults with late-onset Pompe disease. News release. Astellas Pharma Inc; June 26, 2022.

Gene transfer study in patients with late onset Pompe disease (FORTIS). ClinicalTrials.gov. November 22, 2019. Updated April 14, 2022. Accessed June 29, 2022.