Miglustat, part of AT-GAA for LOPD, favored for approval in Europe
EMA committee gives positive recommendation on therapy's 2nd component
Regulatory approval in the European Union for miglustat, a component of the two-part investigational therapy AT-GAA for adults with late-onset Pompe disease (LOPD), has been recommended by a branch of the European Medicines Agency (EMA), the body responsible for monitoring drug therapies in the EU.
A decision on whether or not to approve miglustat, by the European Commission (EC), is expected in the third quarter of this year. Typically, the EC follows recommendations from the EMA’s Committee for Medicinal Products for Human Use (CHMP), which has now favored approval of the oral therapy. If approved, miglustat will be marketed as Opfolda.
“With today’s positive CHMP opinion of Opfolda, we are now one step away from bringing this much-needed new treatment to adults living in Europe with late-onset Pompe disease,” John F. Crowley, executive chairman of AT-GAA developers Amicus Therapeutics, said in a press release,
In March, the EC approved Pombiliti (cipaglucosidase alfa), the treatment’s other component. The therapy’s approval would make it the first two-part therapy for adults with LOPD in the EU, Amicus noted.
“Once fully approved we believe there is significant opportunity to bring Pombiliti and Opfolda as the first two-component therapy for adult LOPD patients in Europe, and to establish this novel treatment combination as a potential new standard of care in Pompe disease,” said Bradley Campbell, president and CEO of Amicus.
Miglustat helps Pombiliti work over time
Pompe disease is caused by insufficient levels of acid alpha-glucosidase (GAA), which results in the toxic buildup of glycogen, a complex sugar molecule. As a result, cells — particularly in the muscle — become damaged.
An enzyme replacement therapy (ERT), Pombiliti is delivered into-the-vein (intravenously) and designed to restore the levels of GAA. Miglustat, meanwhile, stabilizes Pombiliti to maintain its activity over time.
The CHMP’s recommendation, as well as Pombiliti’s approval by the EC, was based on data from the Phase 3 PROPEL trial (NCT03729362). A total of 123 adults with LOPD were enrolled, some new to ERT and others with previous exposure to such treatment. The participants were randomly assigned to either AT-GAA or alglucosidase alfa, an ERT sold in the U.S. as Lumizyme and as Myozyme elsewhere.
Top-line data showed that walking and lung function were improved in patients treated with AT-GAA. The therapy outperformed Lumizyme, though not all differences were statistically significant.
Among the participants, 118 joined an open-label extension (OLE) study (NCT04138277) to begin or continue using AT-GAA. After two years of treatment, the benefits in walking seen in PROPEL with AT-GAA were sustained. Patients who switched to AT-GAA showed stable walking ability. No differences were seen regarding the prior use of ERT.
In patients who had been previously treated with ERT before PROPEL, lung function remained stable during the OLE. Conversely, those treated with Lumizyme in PROPEL showed a decline in lung function, which then remained stable after they moved to AT-GAA in the OLE.
Muscle damage and glycogen buildup also were lessened in patients on AT-GAA.
The CHMP positive opinion and recommended indication reflect this robust body of evidence and gives me further hope for the potential of this innovative therapy for people living with LOPD.
The trial is expected to finish in December.
“In clinical studies, Pombiliti and Opfolda has exhibited clinically meaningful and positive changes in the key manifestations of this challenging disease,” said Benedikt Schoser, professor of neurology at Ludwig-Maximillians-University of Munich, in Germany.
“The CHMP positive opinion and recommended indication reflect this robust body of evidence and gives me further hope for the potential of this innovative therapy for people living with LOPD,” Schoser said.
Both Campbell and Crowley acknowledged the efforts of patients, clinicians, and researchers.
“I am immensely proud of our team that has worked tirelessly over the past decade to develop this innovative therapy,” Campbell said, adding, “We are grateful for the commitment and support from the Pompe community who have helped advance this therapy, especially the patients, families, and physicians who participated in our clinical studies.”
Added Crowley, “This [positive opinion] was the realization of the hard work and efforts of so many individuals dedicated to the mission of improving the lives of people living with Pompe disease.”
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