Rare Daily Staff

The U.S. Food and Drug Administration has extended the review period by 90 days for Amicus Therapeutics Biologics License Application for cipaglucosidase alfa and the New Drug Application for miglustat, the two components of AT-GAA, its experimental treatment for Pompe disease.

The revised PDUFA action dates for miglustat is now August 29, 2022, and for cipaglucosidase alfa is now October 29, 2022. Amicus expects the FDA to approve the applications together.

Pompe disease is an inherited lysosomal disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA levels lead to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. The disease can be debilitating and is characterized by severe muscle weakness that worsens over time. Pompe disease ranges from a rapidly fatal infantile form with significant impacts to heart function to a more slowly progressive, late-onset form primarily affecting skeletal muscle. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide.

AT-GAA is an experimental two-component therapy that consists of cipaglucosidase alfa (ATB200), a unique recombinant human acid alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate structures, particularly bis-phosphorylated mannose-6 phosphate (bis-M6P) glycans, to enhance uptake into cells, administered in conjunction with miglustat (AT2221), a stabilizer of cipaglucosidase alfa. In preclinical studies, AT-GAA was associated with increased levels of the mature lysosomal form of GAA and reduced glycogen levels in muscle, alleviation of the autophagic defect and improvements in muscle strength.

The FDA extended the PDUFA dates to allow additional time to review information submitted by Amicus as part of its ongoing reviews. The extension of the review timeline was not related to requests for any additional clinical data. The company also expects that the additional time will allow for the completion of the pre-license approval inspections necessary at the WuXi Biologics manufacturing site in China.

“We continue to work collaboratively with the FDA as it completes its review of the AT-GAA applications,” said John Crowley, chairman and CEO at Amicus Therapeutics. “We remain deeply committed to bringing AT-GAA to as many people living with Pompe disease as quickly as possible and delivering on our promise to become the potential new standard of care.”

Previously, the FDA granted Breakthrough Therapy designation to AT-GAA for the treatment of late-onset Pompe disease based on clinical efficacy results from the phase 1/2 clinical study. In the European Union, the Marketing Authorization Applications were validated in the fourth quarter of 2021 and the Committee for Medicinal Products for Human Use (CHMP) opinion is expected in late 2022.

Amicus is also enrolling an open-label, uncontrolled, multicenter study to evaluate the psychokinesis, safety, efficacy, and pharmacodynamics of AT-GAA in pediatric patients aged 0 to 18 years with late onset Pompe disease.

Photo: John Crowley, chairman and CEO at Amicus Therapeutics

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