First Late-Onset Pompe Disease Patient Treated With AT-GAA in Phase 3 Trial

Amicus Therapeutics has dosed the first patient in the Phase 3 PROPEL clinical trial that aims to compare investigational therapy AT-GAA (ATB200/AT221) to standard treatment in patients with late-onset Pompe disease.

The trial (NCT03729362) is still recruiting patients. Throughout 2019, approximately 100 participants who have been previously treated with alglucosidase alfa or who have not received any enzyme replacement therapy are expected to be enrolled at 90 different locations worldwide.

Pompe disease is a genetic condition characterized by the impaired activity of the enzyme acid alpha-glucosidase (GAA), which breaks up glycogen in the cells. The lack of GAA leads to glycogen accumulation, followed by muscle weakness and then organ failure.

AT-GAA is an investigational therapy consisting of a human-made GAA variant (rhGAA) — optimized to have a more stable structure — co-administered with a small molecule that acts as a pharmacological chaperone, further stabilizing rhGAA.

Initial results of a Phase 1/2 trial (NCT02675465) showed improved motor and respiratory function and a decrease in muscle damage biomarkers in patients treated with AT-GAA.

The global, double-blind, randomized Phase 3 PROPEL trial will compare the efficacy, safety, and tolerability of AT-GAA with the current standard of care (alglucosidase alfa, an enzyme replacement therapy) in adults with late-onset Pompe disease over a one-year period.

“The initiation of our global PROPEL study is a true example of our capabilities to discover, develop, and manufacture promising therapies, and deliver them to patients as quickly as we can,” John F. Crowley, CEO of Amicus Therapeutics, said in a press release.

“With the first patient treated in this important study, we are now able to provide access to AT-GAA to many more adults with late onset Pompe disease. … People living with Pompe disease are urgently seeking new options, and we hope that the treatment experience in this study will enable global regulatory submissions.”

Two-thirds of the patients will randomly be assigned to receive AT-GAA and one-third will receive the standard care combined with oral placebo. The patients will be treated approximately every two weeks for a year.

After this initial treatment, patients will be eligible to participate in a long-term, open-label extension study.

The primary objective is to assess the improvement in performance in the six-minute walk test from baseline (before receiving treatment) to week 52. Secondary goals include measures of respiratory, pulmonary, and muscle function and muscle strength.

“The PROPEL study provides us with the opportunity to build upon the very compelling data set from the earlier Phase 1/2 clinical study. The PROPEL study is well-designed, with an active comparator arm and several important assessments of efficacy, including the gold standard six-minute walk test. I look forward to treating more patients with AT-GAA in this study,” said Tahseen Mozaffar, MD, chair of neurology at University of California, Irvine, and principal investigator of the trial.

The trial was designed based on feedback from the U.S. Food and Drug Administration and European Medicines Agency. Amicus hopes the results to lead to the approval of AT-GGA for the treatment of patients receiving enzyme replacement therapy as well as patients who have not received any previous treatment.

Amicus also plans to start a smaller study evaluating the effectiveness of AT-GAA in children with Pompe disease this year.