Pombiliti, ERT part of AT-GAA, approved in EU for LOPD
Decision awaited for miglustat, other part of Amicus' combo therapy
Pombiliti (cipaglucosidase alfa), a component of AT-GAA, a two-part investigational therapy, has been approved to treat adults with late-onset Pompe disease (LOPD) in the European Union.
The European Commission (EC) ruling comes on the heels of a positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP), part of the European Medicines Agency.
A CHMP recommendation on the treatment’s other component, oral miglustat, is expected by the end of June. The EC, which makes final approval decisions, typically follows CHMP’s advice.
“The European Commission approval for Pombiliti is another major step towards bringing this much needed, new treatment for all adults living in the EU with late-onset Pompe disease,” John Crowley, executive chairman of Amicus Therapeutics, the therapy’s developer, said in a company press release.
Pombiliti provides a lab-made source of the GAA enzyme lacking in patients
A U.S. Food and Drug Administration (FDA) review of AT-GAA was delayed due to COVID-19 pandemic travel restrictions preventing the inspection of a manufacturing facility in China. An inspection is now scheduled, Amicus reported in March, and approval decisions in the U.S. and the U.K. are anticipated before the year’s end.
The company is providing AT-GAA to LOPD patients via an expanded access program in the U.S., France, Germany, and Japan. U.K. patients might obtain the therapy through an early access to medicines scheme (EAMS).
People with Pompe disease cannot make sufficient amounts of functional acid alpha-glucosidase (GAA), an enzyme that breaks down the complex sugar molecule called glycogen. As a result, glycogen builds to harmful levels and causes damage, especially to muscle cells.
LOPD symptoms develop after the first year of life, and the disease is associated with progressive muscle weakness, especially affecting the torso and legs and, potentially, breathing.
Pombiliti is an enzyme replacement therapy (ERT) administered via infusion into the bloodstream, designed to provide a lab-made source of GAA. Oral miglustat, reviewed separately by regulatory agencies, helps stabilize Pombiliti to maintain its activity over time.
Pombiliti’s use is intended to be in combination with miglustat, Amicus notes.
AT-GAA’s approval applications are primarily supported by data from the Phase 3 PROPEL trial (NCT03729362), which enrolled 123 adults LOPD patients with and without previous ERT exposure. Participants were randomly assigned to either AT-GAA or alglucosidase alfa, the first approved ERT for LOPD, marketed as Lumizyme in the U.S. and as Myozyme elsewhere.
Top-line PROPEL results showed that AT-GAA treatment improved walking ability and lung function in LOPD patients. AT-GAA appeared to outperform Lumizyme/Myozyme, but some differences were not statistically significant. Infusion-related reactions were reported by about a quarter of those receiving either treatment.
Patients who completed PROPEL were eligible to enter an open-label extension (OLE) study (NCT04138277) to begin or continue using AT-GAA to assess long-term outcomes.
Sustained benefits reported with AT-GAA use in ongoing long-term study
Among 118 OLE patients, two years of treatment sustained the improvements in walking abilities seen in PROPEL, and these abilities remained stable for those who switched to AT-GAA in the OLE. Treatment effects for walking abilities were similar regardless of previous ERT exposure.
Lung function was stable throughout the OLE among patients with ERT exposure before PROPEL’s start. It declined among those randomized to Lumizyme/Myozyme in PROPEL, but stabilized after they moved to AT-GAA in the OLE.
AT-GAA’s use also tended to lessen measures of muscle damage and glycogen clearance, Amicus reported. The OLE is expected to conclude in December.
“We are extremely pleased with the EC approval of Pombiliti, an innovative enzyme replacement therapy that is intended for use in combination with the oral enzyme stabilizer miglustat,” said Bradley Campbell, Amicus’ president and CEO. “We are grateful to the Pompe community who have helped advance this therapy, especially the patients, families, and physicians around the world who participated in our clinical studies.”
Should both components be approved, “we look forward to bringing AT-GAA to people in Europe living with LOPD as rapidly as possible,” Campbell added.
Recruitment is underway at the University of Florida for the Phase 3 ROSSELLA trial (NCT04808505), an open-label study to assess the safety and effectiveness of AT-GAA in up to 36 children, from birth through age 16, with infantile-onset Pompe disease.
“Given the strength of the label and our launch readiness, we believe … that AT-GAA has the potential to become the next standard of care in Pompe disease by redefining the therapeutic expectations of people living with Pompe disease and of their caregivers,” Campbell said.
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