AT-GAA Continues to Induce Motor, Lung Improvements in Pompe Adult Patients, Phase 1/2 Study Shows

Amicus Therapeutics’s investigational therapy AT-GAA (ATB200/AT221) continues to show promise as a safe and effective treatment for adults with Pompe disease, according to the latest results from an ongoing Phase 1/2 clinical trial.

Pompe disease is caused by acid alpha-glucosidase (GAA) enzyme deficiency, leading to the build-up of glycogen — a large sugar molecule used for energy storage — in several tissues. It mainly affects skeletal muscle cells, including those involved in breathing, and heart cells.

AT-GAA consists of ATB200, a lab-made human GAA enzyme, in combination with the investigative pharmacological chaperone AT2221, which was developed to stabilize ATB200’s structure.

The international, multi-center, open-label Phase 1/2 clinical trial (NCT02675465), known as ATB200-02, is evaluating the safety, tolerability, and effectiveness of AT-GAA in Pompe disease patients. The study also will assess AT-GAA’s pharmacokinetics (the therapy’s movement in the body) and pharmacodynamics (the therapy’s effects on the body).

Initial results of nine months of treatment in 20 patients showed that AT-GAA improved motor and lung function and reduced the levels of muscle damage biomarkers.

Now, the trial’s 24-month data were disclosed in an oral presentation titled “First-in-Human Study of ATB200/AT2221 in Patients With Pompe Disease: 24-Month Functional Assessment Results From the ATB200-02 Trial,” at the International Annual Congress of the World Muscle Society, held Oct. 1-5 in Copenhagen, Denmark.

The trial initially enrolled 22 Pompe patients, 17 of whom had been treated previously with enzyme replacement therapy (ERT) — 11 patients who were able to walk (group 1) and six patients in wheelchairs, who could not walk anymore (group 2). The remaining five patients were able to walk, but had never been treated with ERT, called ERT-naive (group 3).

A fourth group of six additional patients, who had been treated with ERT for at least seven years and who could still walk, was subsequently added to the study.

Results of the remaining 18 patients of groups 1 to 3 (four of 22 discontinued) showed that 24 months of treatment improved the patients’ muscle strength and motor function — assessed by the 6-minute walk test (6MWT), which measures the distance an individual is able to walk on a hard, flat surface in six minutes.

Patients in group 1 and 3 increased their ability to walk by 36 and 61 meters in the 6MWT, respectively, and patients in wheelchairs increased their upper extremity strength.

Lung function, measured by forced vital capacity (FVC) — the total volume of air that can be blown forcefully following a full inhalation — remained stable in ERT-pretreated patients and was improved in ERT-naive patients (group 3).

Patients in group 4 also showed improvements in muscle strength, motor and lung function after three to 15 months of treatment. Notably, while these patients were having an average decline of approximately seven meters (7.6  yards) per year in the 6MWT while on ERT, they had a mean increase of 19 meters (20.7 yards) at the last data assessment of AT-GAA treatment.

“These new data in the [group] 4 patients are particularly impressive showing the potential for AT-GAA to change the course of the disease in these patients,” said Benedikt Schoser, MD, the ATB200-02 study’s principal investigator.

AT-GAA treatment also led to persistent and durable reductions in key biomarkers of muscle damage and Pompe disease, suggesting it can prevent muscle deterioration.

Regarding safety and tolerability, data from up to 40 months of treatment has shown that adverse events (side effects) have been generally mild and transient. The clinical pharmacokinetic profile has been consistent with that reported in previous preclinical data.

“Compared to what is known about the natural history of both untreated and ERT-experienced patients, these results give great hope that AT-GAA has the potential to become the new standard of care for people living with Pompe,” John F. Crowley, Amicus’s chairman and CEO, said in a press release.

Based on ATB200-02 study’s results, AT-GAA was granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of late-onset Pompe disease.

Crowley added that the data “also provide further support and confidence in the overall study design and powering of our ongoing pivotal PROPEL study.”

The Phase 3 PROPEL clinical trial (NCT03729362) is comparing the clinical benefits of AT-GAA and current standard-of-care therapy (alglucosidase alfa, marketed as Lumizyme and Myozyme) in patients with late-onset Pompe disease. The trial, which is still recruiting, dosed its first patient in January.

Amicus is hopeful the results will lead to the approval of AT-GGA for the treatment of Pompe patients currently receiving ERT or who have received no prior treatment. The company plans to initiate a small open-label study evaluating the effectiveness of AT-GAA in children with Pompe disease.