Posts by: Emily Malcolm, PhD

AT-GAA (ATB200/AT2221) is an investigative treatment being developed by Amicus Therapeutics for Pompe disease. It was granted orphan drug status in 2017 by the U.S. Food and Drug Administration for this disorder. What is Pompe disease? Pompe disease is an inherited lysosomal storage disorder that's caused by mutations in the GAA gene, which provides instructions to build the GAA enzyme. Many types of cells store sugar in the form of a complex carbohydrate molecule called glycogen. In order to use the energy stored in glycogen, cells need GAA to break it down. Without GAA, glycogen builds up within cells and interferes with their function, especially in the heart, lungs, and skeletal muscles, which causes the symptoms associated with Pompe disease. The type of mutation determines age of disease onset and severity. The complete or near-complete loss of enzyme function is associated with the early childhood form of the condition. How does AT-GAA work? AT-GAA consists of an artificially created human GAA enzyme with an optimized structure (ATB200) that's administered with a small molecule pharmacological chaperone (AT2221). ATB200 compensates for the lack of natural GAA enzyme in patients while the chaperone AT2221 stabilizes the structure of ABT200, which would otherwise be partially disrupted during the delivery of the treatment. Chaperones are designed to enhance the structural stability or correct the misfolding of proteins. The co-administration of ATB200 and AT2221 allows the delivery of active functional recombinant GAA to the target cells in the body. The chaperone molecule may also stabilize the misfolded and dysfunctional molecules of the patient's own GAA enzyme and thus partially restore its function. AT-GAA in clinical trials AT-GAA is currently being investigated in an open-label Phase 1/2 clinical trial (NCT02675465) in patients with Pompe disease. The study’s objectives are to evaluate the safety, tolerability, pharmacokinetics (movement in the body), pharmacodynamics (effects on the body), and efficacy of AT-GAA over an 18-week primary treatment period followed by a long-term extension study. The trial enrolled 20 patients, 15 of whom have previously been treated with enzyme replacement therapy (ERT). Preliminary results from the trial showed that patients treated with AT-GAA for up to 12 months showed improvements in motor function as measured by the six-minute walk test (6MWT) and in respiratory function as measured by forced vital capacity (FVC), as well as durable reductions in biomarkers of muscle damage. The 24-month data from these patients and an additional group of six patients, who had been treated with ERT for at least seven years and who could still walk, were presented at the International Annual Congress of the World Muscle Society. The first group of patients still demonstrated improvements in the 6MWT at 24 months. No change in FVC was observed in patients who had previously been treated with ERT, but improvements were seen in previously untreated patients. The additional group of six patients were on AT-GAA for between three and 15 months at the time of the presentation and showed improvement in muscle strength, and motor and lung function. Most notably, these patients had shown a decrease in muscle strength (7.6 yards as measured by the 6MWT) while on ERT, but showed significant improvements (20.7 yards) when treated with AT-GAA. In addition, an ongoing Phase 3 clinical trial (NCT03729362) called PROPEL will compare the clinical benefits of AT-GAA and the current standard-of-care therapy Lumizyme in patients with late-onset Pompe disease. The study aims to recruit 100 patients at 58 locations around the world. Other information The side effects of AT-GAA observed in clinical trials have so far been mild and transitory, with some patients receiving up to 40 months of treatment. Last updated: Oct. 9, 2019 *** Pompe Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Posts by: Emily Malcolm, PhD

Emily Malcolm, PhD

Pompe Disease and Pregnancy

I Have Pompe Disease; Will I Pass It to My Children?