New Analysis of Pombiliti® (cipaglucosidase alfa-atga) + Opfolda® (miglustat) Published in Muscle and Nerve

Rhea-AI Summary

Amicus Therapeutics announced new post-hoc analysis results from the PROPEL study of Pombiliti + Opfolda in late-onset Pompe disease (LOPD), published in Muscle and Nerve. The analysis focused on ERT-experienced patients who switched from alglucosidase alfa to cipaglucosidase alfa-atga + miglustat (cipa+mig). Results showed that patients who switched to cipa+mig (n=65) demonstrated improvements or stability across multiple outcomes, including 6-minute walk distance, muscle testing, and PROMIS-Fatigue scores. In contrast, patients who remained on alglucosidase alfa + placebo (n=30) generally showed worsening or stability. The PROPEL study involved 123 adult LOPD patients, with 77% previously treated with alglucosidase alfa. The findings suggest potential benefits for LOPD patients switching to Pombiliti + Opfolda, particularly in maintaining or improving various functional measures in this progressive condition.

Positive

• Patients switched to cipa+mig showed improvements in 6-minute walk distance, muscle testing, and PROMIS-Fatigue measures
• ERT-experienced patients treated with cipa+mig walked an estimated 17 meters farther than the comparator group
• Patients on cipa+mig showed an estimated treatment difference of 3.5% in FVC compared to the comparator group
• High study completion rate with >95% of patients completing the PROPEL study

Negative

• PROPEL study did not achieve statistical significance for the primary endpoint of superiority in 6-minute walk distance in the overall population
• Treatment carries risks of severe hypersensitivity reactions including anaphylaxis
• Contraindicated in pregnancy due to embryo-fetal toxicity risks
• Potential serious side effects including infusion-associated reactions and acute cardiorespiratory failure in susceptible patients

Insights

Pharmaceutical Research Analyst

New data strengthens Pombiliti+Opfolda's clinical profile in Pompe disease, showing benefits in patients switching from standard therapy.

Amicus Therapeutics has published a post-hoc analysis of the PROPEL study demonstrating that patients with late-onset Pompe disease (LOPD) who switched from the standard enzyme replacement therapy (alglucosidase alfa) to Pombiliti+Opfolda showed improvement or stability across most outcome measures, while those remaining on standard therapy generally showed worsening or stability.

This analysis used a within-group effect-size methodology (Cohen's d) to evaluate treatment effects across various domains. Notably, patients switched to Pombiliti+Opfolda demonstrated significant improvements in several critical measures: 6-minute walk distance, manual muscle testing, PROMIS-Fatigue scores, physician and subject global impression scores, and biomarker levels. Most importantly, no significant worsening was observed in any outcomes for patients on Pombiliti+Opfolda.

The data is particularly meaningful considering that 77% of the PROPEL study participants were experienced ERT users with a median treatment duration of 7.4 years. The stability or improvement seen after switching therapies is clinically relevant in LOPD, which is characterized by progressive muscle weakness and respiratory decline.

While this represents a post-hoc analysis rather than the primary PROPEL study results (which did not achieve statistical significance for the primary endpoint in the overall population), the consistency of benefits across multiple domains strengthens the clinical profile of Pombiliti+Opfolda. For physicians treating LOPD patients experiencing suboptimal outcomes on standard therapy, these results provide evidence supporting the potential benefits of switching to Amicus's two-component therapy.

PRINCETON, N.J., June 03, 2025 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq: FOLD), today announced the publication of a post-hoc analysis of data from the ERT-experienced cohort of the PROPEL study of cipaglucosidase alfa-atga + miglustat (cipa+mig) in adults with late-onset Pompe disease (LOPD) in Muscle and Nerve. In this new publication, based on a within group effect-size analysis, subjects who switched from alglucosidase alfa to cipa+mig achieved improvements or stability in most of the outcomes measured.

In PROPEL, 77% of patients (n=95) received enzyme replacement therapy (ERT) with alglucosidase alfa before study entry, with a median ERT duration of 7.4 years. In this new publication of post-hoc analysis from PROPEL, ERT-experienced patients switched to cipa+mig (n=65), showed improvement (d≥0.2) or stability (−0.2<d<0.2), while those remaining on alglucosidase alfa + pbo (n=30) generally showed within-group worsening (d≤−0.2) or stability (−0.2<d<0.2) across most outcomes. Patients switched to cipa+mig did not demonstrate significant worsening for any outcomes and showed significant improvements for 6-minute walk distance (absolute and % predicted); upper, lower, and overall manual muscle testing; Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue; Physician (overall score) and Subject Global Impression of Change (5/8 subdomains); and biomarker levels. Patients remaining on alglucosidase alfa + pbo demonstrated statistically significant worsening for several lung function outcomes, biomarker levels, and significant improvement for PROMIS-Dyspnea. Additional details of the analysis methodology can be found below.

“Across the different domains in this analysis, patients who switched to Pombiliti + Opfolda experienced stability or improvement on many measures, including 6-minute walking distance and PROMIS-Fatigue, compared to those who remained on alglucosidase alfa who primarily stayed stable or experienced worsening,” said Hani A. Kushlaf, MD, Professor of Neurology and Pathology, University of Cincinnati. “Given that LOPD is a progressive condition, it’s imperative that physicians assess when patients should consider switching to Pombiliti + Opfolda.”

“The consistency of stability or improvement across multiple domains in the cohort of ERT-experienced patients from PROPEL – including measures of biomarkers, muscle strength, motor function, pulmonary function, and quality of life – is highly encouraging in a disease known for its relentless progression,” said Jeff Castelli, PhD, Chief Development Officer, Amicus Therapeutics, Inc. “We view these results as further validation of the differentiated mechanism and clinical profile of Pombiliti + Opfolda and remain committed to advancing therapies that make a tangible difference in the lives of people living with late-onset Pompe disease.”

About the PROPEL Study
PROPEL was a 52-week, double-blind randomized global study designed to assess the efficacy, safety, and tolerability of cipaglucosidase alfa-atga + miglustat compared to non-U.S. approved alglucosidase alfa + placebo (the comparator). The study enrolled 123 adult LOPD patients who still had the ability to walk and to breathe without mechanical ventilation.

Patients enrolled in PROPEL were randomized 2:1 so that for every two patients randomized to be treated with cipaglucosidase alfa-atga + miglustat, one was randomized to be treated with the comparator. Of the patients enrolled in PROPEL, 77% were being treated with alglucosidase alfa (n=95) for at least 2 years at study entry and 23% had never been treated with any ERT (n=28). 117 of the 123 patients (>95%) completed the PROPEL study.

Efficacy endpoints of the study included primary endpoint of change from baseline to week 52 in 6-minute walk distance (6MWD) for comparison of superiority and key secondary endpoint of change from baseline to week 52 in forced vital capacity (FVC). PROPEL did not achieve statistical significance for the primary endpoint of superiority in change from baseline to week 52 in 6MWD in the overall population. After 52 weeks, ERT-experienced patients treated with cipaglucosidase alfa-atga + miglustat (n=61) walked an estimated 17 meters (95% CI, 0.2, 33) farther than the comparator group (n=29). After 52 weeks, ERT-experienced patients treated with cipaglucosidase alfa-atga + miglustat (n=55) showed an estimated treatment difference of 3.5% (95% CI, 1.0, 6.0) in FVC compared with the comparator group (n=29).

More details about this post-hoc analysis
This post-hoc analysis assessed the magnitude of within-group treatment effects across measures of motor function, muscle strength, pulmonary function, patient-reported outcomes/QoL measures, and biomarkers. Standardized effect size analysis describes the absolute effect size relative to the variability of the data. It transforms the effect size into a scale with no units of measurement (Cohen’s d). The authors calculated standardized within-group effect sizes (Cohen’s d for within-group comparisons) and corresponding 95% CIs for the change from baseline to week 52 for the primary, secondary, and pharmacodynamic endpoints of the PROPEL study. Standardized within-group effect sizes and corresponding 95% CIs were calculated by dividing the mean change from baseline values and CIs at week 52 by the standard deviation (SD) of the difference scores. Consistent with medical literature, effect sizes were defined as stable (−0.2 < d < 0.2), small (0.2 ≤ d < 0.5), medium (0.5 ≤ d < 0.8), or large (d ≥ 0.8) improvement, or as small (−0.5 < d ≤ −0.2), medium (−0.8 < d ≤ −0.5), or large (d ≤ −0.8) worsening, and were considered statistically significant if the standardized 95% CIs did not cross zero.

About Pombiliti + Opfolda
Pombiliti^® + Opfolda^®, is a two-component therapy that consists of cipaglucosidase alfa-atga, a bis-M6P-enriched rhGAA that facilitates high-affinity uptake through the M6P receptor while retaining its capacity for processing into the most active form of the enzyme, and the oral enzyme stabilizer, miglustat, that’s designed to reduce loss of enzyme activity in the blood.

U.S. INDICATIONS AND USAGE
POMBILITI in combination with OPFOLDA is indicated for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).

SAFETY INFORMATION

HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS: Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, POMBILITI should be discontinued immediately and appropriate medical treatment should be initiated. INFUSION-ASSOCIATED REACTIONS (IARs): If severe IARs occur, immediately discontinue POMBILITI and initiate appropriate medical treatment. RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS: Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function, may be at risk of serious exacerbation of their cardiac or respiratory status during POMBILITI infusion. See PI for complete Boxed Warning. CONTRAINDICATION: POMBILITI in combination with Opfolda is contraindicated in pregnancy. EMBRYO-FETAL TOXICITY: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 60 days after the last dose. Adverse Reactions: Most common adverse reactions ≥ 5% are headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia. Please see full PRESCRIBING INFORMATION, including BOXED WARNING, for POMBILITI (cipaglucosidase alfa-atga) LINK and full PRESCRIBING INFORMATION for OPFOLDA (miglustat) LINK.

About Late-Onset Pompe Disease
Late-onset Pompe disease is an inherited lysosomal disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA lead to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. Late-onset Pompe disease can be severe and debilitating with progressive muscle weakness throughout the body that worsens over time, particularly skeletal muscles and muscles that control breathing.

About Amicus Therapeutics
Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a pipeline of cutting-edge, first- or best-in-class medicines for rare diseases. For more information please visit the company’s website at www.amicusrx.com, and follow on X and LinkedIn.

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CONTACTS:

Investors:
Amicus Therapeutics
Andrew Faughnan
Vice President, Investor Relations
afaughnan@amicusrx.com
(609) 662-3809

Media:
Amicus Therapeutics
Diana Moore
Vice President, Corporate Communications
dmoore@amicusrx.com
(609) 662-5079

FOLD–G

FAQ

What are the main findings of the new Pombiliti + Opfolda PROPEL study analysis for FOLD stock?

The analysis showed that LOPD patients who switched to Pombiliti + Opfolda demonstrated improvements or stability in multiple outcomes, while those remaining on alglucosidase alfa generally showed worsening or stability across most measures.

What is the effectiveness of Pombiliti + Opfolda compared to previous treatments?

ERT-experienced patients treated with Pombiliti + Opfolda walked an estimated 17 meters farther and showed a 3.5% better FVC compared to the comparator group after 52 weeks.

What are the main safety concerns for Amicus Therapeutics' Pombiliti + Opfolda?

Key safety concerns include risks of hypersensitivity reactions including anaphylaxis, infusion-associated reactions, acute cardiorespiratory failure in susceptible patients, and embryo-fetal toxicity.

How many patients were involved in the PROPEL study for FOLD's Pombiliti + Opfolda?

The PROPEL study enrolled 123 adult LOPD patients, with 77% (95 patients) previously treated with alglucosidase alfa and 23% (28 patients) who were ERT-naive.

What is the specific indication for Amicus Therapeutics' Pombiliti + Opfolda treatment?

Pombiliti + Opfolda is indicated for treating adult patients with late-onset Pompe disease weighing ≥40 kg who are not improving on their current enzyme replacement therapy.