#MDA2022 – AT-GAA Improves Walking, Lung Function, 3-year Data Show
Treatment with the two-part investigational therapy AT-GAA improved walking ability and lung function for up to three years among adults with Pompe disease in a Phase 1/2 clinical trial.
Barry Byrne, MD, PhD, from the University of Florida, presented the findings at the 2022 MDA Clinical & Scientific Conference, in a talk titled “Long-term Follow-up of Cipaglucosidase Alfa/Miglustat in Ambulatory Patients with Pompe Disease: an Open-label Phase I/II Study (ATB200-02).” The research was supported by Amicus Therapeutics, the company developing AT-GAA.
Pompe disease is caused by mutations in the gene coding for the enzyme acid alpha-glucosidase, which is needed to break down a complex sugar molecule called glycogen. AT-GAA is a two-component therapy containing cipaglucosidase alfa, an optimized version of this enzyme, as well as a molecule called miglustat which helps stabilize the enzyme.
Amicus is sponsoring a Phase 1/2 clinical trial called ATB200-02 (NCT02675465) to evaluate AT-GAA’s safety and effectiveness. The study enrolled 23 adults with Pompe disease who were able to walk and six who could not walk, all of whom were treated with the experimental medication. Among the participants, 23 had previously been on enzyme-replacement therapy (ERT), and the other six had not. Among the group who could walk, six patients had used ERT for at least seven years, and 11 had been on ERT for up to six years.
After increasing doses of cipaglucosidase alfa in the study’s first stage of six weeks, two doses of miglustat were assessed in stage two (which lasted 12 weeks). In the ongoing stage three, which has two years of data, cipaglucosidase alfa is used at 20 mg/kg and miglustat at 260 mg, determined to be the most effective doses and given every two weeks.
Among the assessments used in the study were six-minute walk distance (6MWD), a common measure of exercise ability in people who are able to walk, and forced vital capacity (FVC), a measure of lung function. Assessments of muscle function also were reported. Participants have been followed for up to three years.
Results showed that 6MWD scores improved significantly with AT-GAA treatment, regardless of whether patients had previously been on ERT.
Specifically, among 16 patients who had been on ERT previously, mean 6MWD scores increased by 23.1 meters (about 76 feet) after six months on AT-GAA. In eight patients previously on ERT who were on AT-GAA for three years, mean 6MWD score improved by 47.8 meters (157 feet).
Similarly, among five patients who had not been on prior ERT, mean 6MWD score increased by 43.5 meters (143 feet) after three years on AT-GAA.
“Even greater than 25 meters would be clinically meaningful, so this is quite encouraging,” Byrne said.
Among patients on prior ERT, FVC scores were generally stable throughout the trial. This contrasts the natural course of Pompe disease; in the absence of treatment, FVC would be expected to gradually worsen over time as the disease progresses.
In ERT-naïve patients (those who had not been on ERT), FVC scores increased significantly with AT-GAA treatment — by a mean of 6.2% after three years, based on data from five participants.
Muscle strength tests of participants’ legs showed that AT-GAA treatment led to a “small, positive increase in both ERT-naïve and ERT-experienced patients,” Byrne said. He noted that the increases were somewhat greater in patients who had not been on prior ERT, and that improvements were sustained out to three years of treatment.
Safety data were generally similar to what is seen for existing ERT treatments, and were similar among participants, regardless of their prior ERT use.
“That really is reassuring, that this combination therapy, this two-component therapy actually has a safety profile consistent with existing therapy,” Byrne said.
The most common treatment-related safety issues were infusion reactions, which was the reason cited by one participant for withdrawing from the study.
Biomarker data broadly suggested that AT-GAA treatment led to a reduction in glycogen levels in the body. These data “will be useful in long-term follow-up of patients,” Byrne said.
AT-GAA is currently being reviewed as a potential Pompe treatment in the U.S. and in the European Union. Amicus’ applications for AT-GAA are supported by data from the ATB200-02 study, as well as data from a larger Phase 3 clinical trial called PROPEL (NCT03729362).
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