Next-generation therapy may help babies with Pompe live longer, better

Treatment with Nexviazyme (avalglucosidase alfa), a next-generation enzyme replacement therapy from Sanofi, may help babies with infantile-onset Pompe disease live longer without the need for a breathing machine.

Those are the “positive results” seen with the therapy’s use in a late-stage clinical study dubbed Baby-COMET (NCT04910776), which has “met all primary and secondary endpoints,” or goals, Sanofi stated in a company press release.

The developer plans to use these results to apply for approval in the U.S. later this year to expand Nexviazyme’s label to include patients with this form of Pompe. The treatment is now approved in the country to treat individuals ages 1 and older with late-onset Pompe.

“These positive results offer the potential to expand access of Nexviazyme to more patients and families facing a condition with limited treatment options in the earliest months of life,” said Christopher Corsico, MD, global head of development at Sanofi.

The company plans to share the findings on July 8 at the 19th International Congress on Neuromuscular Diseases, being held next week in Florence, Italy.

The new data come from an open-label Phase 3 study that tested how well Nexviazyme works in babies ages 0 to 1 year with infantile-onset Pompe. The main goal was to assess the proportion of previously untreated patients who remained alive and free of invasive ventilation after 52 weeks, or one year, of treatment.

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A rare genetic disease, Pompe is caused by a deficiency of an enzyme called acid alpha-glucosidase (GAA). This enzyme helps break down glycogen, a stored form of sugar. When it is missing or does not work properly, glycogen builds up to toxic levels inside cells, especially muscle cells, and damages them.

In infantile-onset Pompe, GAA is barely active, and symptoms appear within the first few months of life. Babies may feed poorly due to muscle weakness, grow slowly, and have difficulty breathing. Heart problems are also common. Without treatment, most babies develop breathing or heart failure in the first two years of life.

“Infantile-onset Pompe disease is a devastating, rapidly progressive condition that presents within the first days or weeks of life, making early intervention critical to help improve invasive ventilator-free survival beyond one year,” said Priya S. Kishnani, MD, chief of the division of medical genetics at Duke University Medical Center in North Carolina.

Baby-COMET assessed Nexviazyme’s use in 17 infants

Nexviazyme is an enzyme replacement therapy that provides an engineered form of GAA to muscle cells intravenously, or through infusion into the bloodstream. Once inside the muscle cells, the enzyme breaks down glycogen, easing Pompe symptoms.

In Europe, where the therapy is marketed as Nexviadyme, it’s approved to treat both infantile-onset and late-onset Pompe. In the U.S., however, it is only approved for patients with the less severe form of the disease.

In the Baby-COMET clinical study, 17 babies with infantile-onset Pompe were given Nexviazyme at a dose of 40 mg per kilogram of body weight every two weeks. After a four-week screening period, treatment continued for one year, with the option to keep receiving Nexviazyme for as long as approximately three more years.

The Baby-COMET study shows the potential of [Nexviazyme] to support ventilator-free survival in infants, alongside encouraging cardiac and motor outcomes.

The main goal was to measure how many treatment-naïve babies 6 months of age or younger were still alive and did not need invasive ventilation to help with breathing after 12 months on Nexviazyme. As secondary goals, researchers are also looking at survival without invasive ventilation at 12 and 18 months, as well as changes in heart size and motor skills.

All main and secondary goals were met. Nexviazyme was generally well tolerated. There were no serious side effects linked to the treatment, and none of the patients stopped treatment. Infusion-related reactions were reported in 29% of patients, but these side effects were manageable.

“The Baby-COMET study shows the potential of [Nexviazyme] to support ventilator-free survival in infants, alongside encouraging cardiac and motor outcomes, offering important insights that may help advance the treatment landscape for these patients,” said Kishnani, who is also medical director of Duke’s Y.T. and Alice Chen Pediatric Genetics and Genomics Center.