FDA Defers Action on Amicus Filing

Rare Daily Staff

The U.S. Food and Drug Administration has deferred action on the Biologics License Application for Amicus Therapeutics experimental Pompe disease therapy AT-GAA due to an inability to inspect a manufacturing site in China during the review cycle, the company said.

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 investigational 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.

The biologic component of AT-GAA—cipaglucosidase alfa— is produced at a WuXi Biologics manufacturing site in China. Due to restrictions on travel related to COVID-19, the FDA was unable to conduct the required inspection the site.

Amicus said it expects the FDA to approve the two components of AT-GAA, including the BLA and New Drug Application for miglustat, together.

While both applications remain under review, the FDA has not provided anticipated action dates as they continue to monitor the public health situation and travel restrictions in China. The company is now actively engaged with the FDA on developing plans and logistics for a pre-approval inspection plan.

“We are now one step away from the necessary approvals for AT-GAA in the U.S. We continue to believe this is a question of ‘when’ not ‘if’ AT-GAA will be approved and we will continue to work with great urgency to support the FDA’s completion of the final plant inspection necessary for approval so that this important new treatment option is made available for people living with Pompe disease in the United States,” said Bradley Campbell, president and CEO at Amicus Therapeutics.

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, where a pre-approval inspection is not required, the regulatory review is on track and the Committee for Medicinal Products for Human Use (CHMP) opinion is expected before year end.

Photo: Bradley Campbell, president and CEO at Amicus Therapeutics