5 years strong: Combo LOPD therapy preserves walking and lung function

Long-term treatment with the combination therapy Pombiliti + Opfolda (cipaglucosidase alfa and miglustat) helps people with late-onset Pompe disease preserve their walking ability and lung function for at least five years, new clinical trial data show.

Biomarin Pharmaceutical, which markets Pombiliti + Opfolda after acquiring the therapy’s developer Amicus Therapeutics earlier this year, shared the five-year findings at the recent 31st Annual Congress of the World Muscle Society in Hiroshima, Japan.

“These five-year results demonstrate that POMBILITI and OPFOLDA can provide durable, long-term benefits for people living with late-onset Pompe disease, including those who had been on enzyme replacement therapy for years before enrolling in the study,” Greg Friberg, MD, executive vice president and chief research and development officer at Biomarin, said in a company press release.

LOPD is a rare genetic disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme required to break down glycogen, a complex sugar. Without enough GAA, glycogen builds up to toxic levels inside cells, particularly muscle cells that normally rely on glycogen as a way to store sugar. Over time, this causes progressive muscle weakness, making it increasingly difficult to walk and breathe. LOPD is a progressive disorder, meaning that without treatment, symptoms typically worsen over time.

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Pombiliti + Opfolda is a combination therapy that consists of a working version of the GAA enzyme given alongside a small molecule that stabilizes the enzyme. In the U.S. and elsewhere, it is approved to enhance walking ability and improve or stabilize respiratory function.

The approvals were largely based on results from the Phase 3 PROPEL trial (NCT03729362). The newly presented findings track 82 participants who started the combination therapy during PROPEL and continued receiving it for up to five years in an extension study.

Researchers evaluated two main measures of physical health: percent-predicted six-minute walk distance (pp6MWD, a test measuring how far a person can walk in six minutes compared to healthy peers of the same age and height) and percent predicted forced vital capacity (ppFVC, a lung test measuring how much air a person can forcefully exhale in one breath). Both measures are expressed as percentages relative to what’s expected for someone of a given age, sex, height, and ethnicity.

Among participants who had previously received other enzyme replacement therapies before switching to Pombiliti + Opfolda (62 patients), walking scores improved by an average of 0.7% after five years. In the other 20 patients who had not been on prior treatment, pp6MWD improved by a mean of more than 10% after 4.5 years of Pombiliti + Opfolda.

Lung function declined slowly over five years across both groups, falling by an average of 2.8% in previously treated patients and 4.4% in patients who had not received prior treatment.

“Sustaining motor function and limiting pulmonary decline for up to five years in a progressive disease like LOPD is clinically meaningful, and we remain committed to continuing to share long-term evidence to inform the care of people with this rare genetic condition,” Friberg said.

A total of 42 participants experienced treatment-related side effects, most of which were mild to moderate. Five patients stopped treatment due to safety concerns, including two cases of serious treatment-related adverse events — chills and low oxygen levels in one patient, and a body-wide reaction in another. Researchers noted that no new safety risks emerged during the extended five-year monitoring period.