Trial for adults with late onset Pompe disease halted due to serious adverse event

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The US Food and Drug Administration (FDA) has placed a clinical hold on a trial being run for Astrellas Pharma Inc after one of the participants had a serious adverse event (SAE) of peripheral sensory neuropathy.

Astrellas made the announcement after the trial, which is evaluating AT845, an investigational adeno-associated virus (AAV) gene replacement in adults with Pompe disease, was stopped.

Medical significance

The FDA said it did not have enough information to assess the risks to those taking part and more information concerning the SAE was needed. Until now, the SAE has been classified by the investigator as grade one – mild in severity – and now deemed serious because of medical significance. A written notice is expected to be sent from the FDA to Astrellas within 30 days.

Astrella is working with the site investigator to closely follow the patient and will carry on gathering and reviewing all relevant data. All those currently enrolled will continue to be monitored closely.

Weston Miller, senior medical director of clinical development at Astellas Gene Therapies, said: “Patient safety is our top priority, and we are working closely with the FDA to determine appropriate next steps.

“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.”

Genetic medicines

Astellas is focused on developing genetic medicines and working alongside its partners to build a portfolio of potentially life-changing gene therapies.

The company says it strives to identify, develop and deliver therapies for patients with genetic diseases who currently have few or no effective treatment options.

Astellas is reviewing the potential financial impacts of the situation on the fiscal year ending March 31, 2023.

Pompe disease is a rare, severe, autosomal recessive metabolic disease characterized by progressive muscular degeneration. The overall incidence is estimated to be approximately 1 in 40,000 births, although frequency and disease progression varies with age of onset, ethnicity and geography.

It is caused by mutations in a gene that makes an enzyme called acid alpha-glucosidase (GAA).  Normally, the body uses GAA to break down glycogen, a stored form of sugar used for energy. 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.

Chronic treatment

Enzyme replacement therapy, which is a chronic treatment, is the only one currently approved for Pompe disease. It is delivered in bi-weekly infusions and completely relies on the body’s tissue uptake of GAA from plasma.

Astrellas has been developing AT845 as a treatment, a novel gene replacement therapy using an AAV8 vector under a muscle-specific promotor to deliver a functional copy of the GAA gene that is efficiently transduced to express GAA directly in tissues affected by the disease, including skeletal and cardiac muscle.

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