Opfolda joins Pombiliti in treating LOPD patients across EU
Two-part late-onset Pompe disease therapy once known as AT-GAA approved
The enzyme stabilizer Opfolda (miglustat), one part of the two-component therapy formerly known as AT-GAA (cipaglucosidase alfa/miglustat), has been approved by the European Commission to treat adults with late-onset Pompe disease (LOPD).
The news comes a few months after the other part of AT-GAA, the enzyme replacement Pombiliti (cipaglucosidase alfa), was approved for LOPD in Europe.
The combination of Pombiliti plus Opfolda soon will be available for patients in Germany, according to Amicus Therapeutics, the treatment’s developer. The company also will begin the process for establishing reimbursement deals in other European Union countries.
“The European Commission approval for Pombiliti and Opfolda is the realization of the work of so many individuals and teams … We look forward to bringing this much needed, new treatment to all adults living in the EU with late-onset Pompe disease,” John F. Crowley, executive chairman of Amicus, said in a company press release.
Late-onset Pompe disease treatment under review for approval in US, UK
Bradley Campbell, the company’s president and CEO, added: “We believe Pombiliti and Opfolda has the potential to become the next standard of care in this devastating condition by showing that improvement is possible for people living with late-onset Pompe disease.”
The Pombiliti and Opfolda combo is being considered for approval in the U.S. and the U.K.; decisions in both countries are expected before the end of the year.
Pompe disease is caused by deficiency in the enzyme acid alpha-glucosidase (GAA) that works to break down a complex sugar molecule called glycogen, which cells use as a source of energy. Without a working version of this enzyme, glycogen builds to toxic levels in cells, especially in muscle cells, driving disease symptoms.
Pombiliti contains a version of the GAA enzyme given via infusion into the bloodstream, while Opfolda is an orally available stabilizer designed to help maintain the enzyme’s activity.
Approval of the combination therapy in Europe was based mainly on data from the Phase 3 clinical trial PROPEL (NCT03729362), which compared Pombiliti plus Opfolda against the approved enzyme replacement therapy alglucosidase alfa, sold as Lumizyme in the U.S. and as Myozyme elsewhere.
PROPEL trial results showed that treatment with Pombiliti plus Opfolda led to significant improvements in measures of exercise ability and lung function. Findings with the combination therapy tended to be better than with the older enzyme replacement, but some differences did not reach statistical significance, meaning it’s mathematically plausible the difference could be due to chance.
Phase 3 trial of Pombiliti-Opfolda enrolling infantile-onset Pompe patients
“In clinical studies, Pombiliti and Opfolda have exhibited clinically meaningful and positive changes in the key mobility and respiratory manifestations of this challenging disease. The [European Commission] approval and indication reflect the hope for the potential of this innovative therapy for people living with Pompe disease,” said Benedikt Schoser, MD, a professor of neurology at Ludwig Maximilian University in Germany.
Amicus is running a Phase 3 trial called ROSSELLA (NCT04808505) testing the combination therapy in children with infantile-onset Pompe disease. The study is recruiting eligible patients, newborns through 17-year-olds, at the University of Florida Clinical Research Center.
“The Pompe community is greatly appreciative of Amicus’ long-standing commitment to develop a treatment option to address the continuing unmet needs of people living with late-onset disease. Each person deserves alternatives to help them best manage their condition,” said Tiffany House, president of the International Pompe Association.
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