Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation to Amicus Therapeutics’ AT-GAA for the treatment of late onset Pompe disease, an inherited lysosomal storage disorder.

Pompe disease is caused by a genetic mutation that results in a deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA leads to accumulation of glycogen in cells, which causes damage throughout the body. 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.

AT-GAA is an experimental therapy that consists of ATB200, a unique recombinant human acid alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate structures to enhance uptake, co-administered with AT2221, a pharmacological chaperone. In preclinical studies, AT-GAA was associated with increased tissue enzyme levels, reduced glycogen levels in muscle, and improvements in muscle strength. A global Phase 1/2 study (ATB200-02) is ongoing to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of AT-GAA.

AT-GAA is the first ever investigational product for Pompe disease to receive Breakthrough Therapy designation. The designation was instituted by the FDA in 2012 to expedite the development and review of drugs that target serious conditions. To receive the designation there must be preliminary clinical evidence indicating that the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies. The designation includes all of the Fast Track program features, as well as more intensive FDA guidance and discussion. 

The designation for AT-GAA is based on clinical efficacy results from the ongoing ATB200-02 phase 1/2 clinical study, including improvements in six-minute walk distance in late onset Pompe patients and comparison to the natural history of treated patients.

“There is an urgent need for new, second generation therapies for people living with lysosomal storage disorders, especially in a disease like Pompe,” said John Crowley, chairman and CEO of Amicus Therapeutics.

Amicus has initiated PROPEL, a global Phase 3 clinical study of AT-GAA in adult patients with late onset Pompe disease. PROPEL is a 52-week, double-blind randomized study designed to assess the efficacy, safety, and tolerability of AT-GAA compared to the current standard of care, alglucosidase alfa, an enzyme replacement therapy.

Photo: John Crowley, Chairman and CEO of Amicus Therapeutics