Decisions on AT-GAA Pompe disease treatment are likely this year

Regulators in US, UK expected to decide by fall on whether to approve

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Regulatory authorities in the U.S. and the U.K. are expected to decide in the third quarter of this year whether or not to approve AT-GAA as a treatment for late-onset Pompe disease, according to its developer, Amicus Therapeutics.

The U.S. Food and Drug Administration (FDA) had previously delayed its review of AT-GAA because the agency had been unable to inspect a manufacturing facility in China owing to travel restrictions due to the COVID-19 pandemic. That inspection has now been scheduled, Amicus announced in a company press release.

Amicus also has submitted the experimental Pompe disease treatment for approval in both the European Union and the U.K. The Committee for Medicinal Products for Human Use (CHMP), a part of the European Medicines Agency, already adopted a positive opinion for the therapy’s enzyme replacement part, branded as Pombiliti.

A CHMP opinion on miglustat, the treatment’s other part, is expected in the second quarter of this year. The European Commission, which makes final decisions on approvals in the EU, tends to follow recommendations from the CHMP.

“In 2023, we remain laser focused” on a trio of goals, said Bradley Campbell, president and CEO Amicus, naming one as “preparing for the expected approvals and launches of AT-GAA for Pompe disease in multiple major markets.”

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Decisions expected in third quarter on Pompe disease treatment

AT-GAA is a two-part treatment for late-onset Pompe disease — and both components are being reviewed separately in regulatory submissions. One part is a lab-made form of the GAA enzyme cipaglucosidase alfa that is defective or absent in Pompe disease. The other component is a compound known as miglustat that helps to stabilize the enzyme.

While the regulatory applications are being reviewed, Amicus is continuing to provide AT-GAA to patients with LOPD through an expanded access program in the U.S., Germany, France, and Japan. In the U.K., patients can access the therapy through an early access to medicines scheme or EAMS. According to Amicus, “multiple physicians have requested access [to AT-GAA] from each of the leading Pompe centers” in the U.K.

Amicus’ applications for AT-GAA are supported mainly by data from a Phase 3 study called PROPEL (NCT03729362). That study enrolled 123 adults with LOPD who were randomly assigned to treatment with either AT-GAA or alglucosidase alfa, an approved therapy marketed in the U.S. as Lumizyme. Also an enzyme replacement therapy, it is now the standard treatment for late-onset Pompe disease.

Results from that study indicated that AT-GAA treatment could improve walking ability and lung function in LOPD. Trends generally favored AT-GAA over Lumizyme, but not all differences between the two treatments were statistically significant. Both medicines had generally similar safety profiles, with injection-associated reactions reported in about a quarter of participants receiving either treatment.

Those who completed the PROPEL study had the option to enroll in an open-label extension trial (NCT04138277), in which all are being treated with AT-GAA and followed for long-term outcomes. New results from the extension trial were presented at the 19th Annual WORLDSymposium on Feb. 26 and announced in a separate press release from Amicus.

These data covered 118 patients who had been on the therapy for two years (104 weeks). Among the patients, 28 had not received the enzyme replacement before entering the PROPEL study.

Improvement in walking ability seen with AT-GAA during the initial study was sustained out to two years of treatment, the results showed. Also, walking ability remained stable for patients who switched from Lumizyme to AT-GAA. The effect on walking ability was generally similar regardless of whether or not patients had previously been on enzyme replacement, the data showed.

These [extension study] results give great hope that AT-GAA has the potential to become the new global standard of care for people living with Pompe disease.

Among patients who had been on enzyme replacement before entering PROPEL, measures of lung function were stable throughout the open-label extension for patients on AT-GAA. For those on Lumizyme in the initial study, lung function tended to decline while on the older therapy, but then stabilized after switching to AT-GAA in the open-label extension.

Patients who had not been on enzyme replacement previously tended to experience a slight decline in lung function during the initial PROPEL study, regardless of which therapy they were given. Lung function measures generally stabilized in these patients during the open-label extension when all were on AT-GAA, according to Amicus.

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No new safety issues were identified in the open-label extension, and biomarker measures of muscle damage and glycogen clearance tended to show favorable effects with AT-GAA treatment. Glycogen is a complex sugar molecule that accumulates to toxic levels in the cells of Pompe patients.

“These open label extension data from our Phase 3 PROPEL study of AT-GAA continue to represent meaningful and durable improvements in functional outcomes, as well as persistent reductions in key biomarkers of muscle damage and disease substrate out to two years,” Campbell said, adding, “These results give great hope that AT-GAA has the potential to become the new global standard of care for people living with Pompe disease.”

According to Benedikt Schoser, MD, the principal investigator on the PROPEL study, “these first long-term results suggest that AT-GAA treatment for up to two years was associated with a durable effect.”

“This new data set could support a long-term treatment benefit in people with late-onset Pompe disease,” added Schoser, from Ludwig-Maximilians-University of Munich, in Germany.

Amicus also is conducting a clinical trial called ROSSELLA (NCT04808505) to test the safety and effectiveness of AT-GAA in children with infantile-onset Pompe disease (IOPD). That study is now recruiting children at a center in Florida. All children enrolled will be treated with AT-GAA.