Benefits of Pombiliti + Opfolda last for years, new data show
Treatment sustained improvements in motor function, biomarkers over 4 years
For adults with late-onset Pompe disease (LOPD), Pombiliti + Opfolda (cipaglucosidase alfa/miglustat) appears to offer lasting benefits.
New four-year data from a Phase 3 trial show the combination treatment helped sustain improvements in motor function and disease biomarkers in patients who had previously been treated with standard enzyme replacement therapy (ERT). The findings, from a new analysis of the Phase 3 PROPEL trial (NCT03729362) and its open-label extension (OLE) study (NCT04138277), may offer hope for those seeking a more effective and durable treatment for the progressive muscle-wasting condition.
Developer Amicus Therapeutics discussed the results in a presentation, titled “208-week efficacy and safety of cipaglucosidase alfa plus miglustat in patients with late-onset Pompe disease treated from PROPEL baseline: muscle function and biomarkers,” at the International Congress of Inborn Errors of Metabolism, held recently in Kyoto, Japan.
What the new analysis shows
“This new analysis adds to the growing body of evidence supporting the compelling clinical profile of Pombiliti and Opfolda” in adults previously treated with ERT, Jeff Castelli, PhD, chief development officer for Amicus, said in a company press release. “We look forward to presenting long-term extension data across pulmonary [lung function] measures soon and will continue to closely study Pombiliti and Opfolda as part of our commitment to make a meaningful difference in the lives of people living with late-onset Pompe disease.”
In LOPD, the large sugar molecule glycogen accumulates in cells due to a lack of functional acid alpha-glucosidase, the enzyme that usually breaks it down. Glycogen buildup leads to muscle damage and symptoms such as muscle weakness, breathing issues, and heart problems.
Standard ERTs, including Sanofi’s Lumizyme (alglucosidase alfa; sold as Myozyme outside the U.S.), work to supply the body with a version of the missing enzyme via routine infusions into the bloodstream, facilitating glycogen breakdown to ease symptoms.
Pombiliti + Opfolda is a combination therapy that includes the ERT cipaglucosidase alfa (Pombiliti) and an oral small molecule called miglustat (Opfolda) that stabilizes the enzyme and helps it stay active longer in the bloodstream. It is approved in the U.S. for adults with LOPD who are not improving on their current ERT.
PROPEL enrolled 123 adults with LOPD, about three-quarters of whom had previously been on Lumizyme (ERT-experienced), while the remaining participants had never received ERT (ERT-naive). Participants were randomly assigned to receive Pombiliti + Opfolda or Lumizyme for about a year.
Results showed Pombiliti + Opfolda outperformed Lumizyme for improving physical function, as assessed by the six-minute walk distance (6MWD) test. Still, the difference was only statistically significant in the subset of ERT-experienced participants.
The treatment combination was also associated with slower declines in lung function and reductions in disease biomarkers.
After completing the main trial, 118 participants entered the OLE, where all continued receiving long-term Pombiliti + Opfolda. Previous analyses showed the benefits of the treatment combination were generally sustained for two years of treatment.
Motor function and biomarkers
The recent analysis covered four years of data from the trials, focusing mainly on the 62 ERT-experienced participants who had used Lumizyme for a median of 7.5 years before being assigned to receive Pombiliti + Opfolda at PROPEL’s start.
The data showed that after four years, the predicted 6MWD had improved by a mean of 2.3% from the start of PROPEL.
Moreover, scores on other muscle strength and physical function measures, including the lower extremity manual muscle test, Gait-Stairs-Gowers-Chair test, and the PROMIS physical function score, were all generally stable or improved since the start of the main study.
Blood levels of creatine kinase, a marker of muscle damage, were reduced, as were levels of urine hexose tetrasaccharide, a biomarker that reflects the degree of glycogen accumulation.
Seeing such sustained improvements or stabilizations “is very encouraging given the progressive nature of LOPD,” Castelli noted.
No new safety signals were identified. According to Amicus, lung function data from the OLE will be presented at an upcoming conference.
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