New 4-Year Data for Pombiliti® (cipaglucosidase alfa-atga) + Opfolda® (miglustat) Presented at ICIEM
Amicus Therapeutics (Nasdaq: FOLD) presented new 4-year data from the PROPEL open-label extension study of Pombiliti® + Opfolda® in adults with late-onset Pompe disease (LOPD). The analysis focused on 82 patients, including 62 ERT-experienced and 20 ERT-naïve individuals.
Key findings in ERT-experienced patients after 208 weeks showed improvements across multiple metrics: +2.3% in six-minute walk distance, +1.6 points in lower extremity manual muscle test score, and notable improvements in other functional measures. The treatment demonstrated a favorable safety profile with no new safety signals identified, though 41 patients experienced treatment-related adverse events.
The data supports the durability and efficacy of Pombiliti + Opfolda in treating LOPD patients who are not improving on current enzyme replacement therapy (ERT).
Amicus Therapeutics (Nasdaq: FOLD) ha presentato nuovi dati a 4 anni dallo studio di estensione in aperto PROPEL su Pombiliti® + Opfolda® in adulti con malattia di Pompe a esordio tardivo (LOPD). L'analisi ha incluso 82 pazienti, di cui 62 con precedente terapia sostitutiva enzimatica (ERT) e 20 naive alla ERT.
I risultati principali nei pazienti con precedenti ERT, dopo 208 settimane, hanno mostrato miglioramenti in diverse misure: +2,3% nella distanza percorsa al test dei sei minuti, +1,6 punti nel punteggio del test manuale della forza degli arti inferiori, oltre a rilevanti progressi in altre valutazioni funzionali. Il trattamento ha mostrato un profilo di sicurezza favorevole senza nuovi segnali di sicurezza identificati, sebbene 41 pazienti abbiano riportato eventi avversi correlati al trattamento.
I dati supportano la durabilità e l'efficacia di Pombiliti + Opfolda nel trattamento dei pazienti LOPD che non migliorano con l'attuale terapia sostitutiva enzimatica (ERT).
Amicus Therapeutics (Nasdaq: FOLD) presentó nuevos datos a 4 años del estudio de extensión abierto PROPEL de Pombiliti® + Opfolda® en adultos con enfermedad de Pompe de inicio tardío (LOPD). El análisis se centró en 82 pacientes, incluidos 62 con experiencia previa en ERT y 20 sin tratamiento con ERT.
Los hallazgos clave en pacientes con experiencia en ERT tras 208 semanas mostraron mejoras en varias métricas: +2,3% en la distancia de la prueba de marcha de seis minutos, +1,6 puntos en la puntuación del test manual de fuerza de las extremidades inferiores, y mejoras destacables en otras medidas funcionales. El tratamiento mostró un perfil de seguridad favorable sin nuevas señales de seguridad identificadas, aunque 41 pacientes presentaron eventos adversos relacionados con el tratamiento.
Los datos respaldan la durabilidad y eficacia de Pombiliti + Opfolda en el tratamiento de pacientes con LOPD que no mejoran con la terapia de reemplazo enzimático (ERT) actual.
아미커스 테라퓨틱스 (Nasdaq: FOLD)는 후기 발병 포메 병(LOPD) 성인에서 Pombiliti® + Opfolda®의 PROPEL 공개확장 연구에 대한 신규 4년 데이터를 발표했습니다. 분석에는 이전에 ERT를 받은 62명과 ERT 미경험 20명을 포함한 82명의 환자가 포함되었습니다.
ERT 경험 환자에서 208주 후 주요 결과는 여러 지표에서 개선을 보였습니다: 6분 보행거리 +2.3%, 하지 근력 수동검사 점수 +1.6점 등 다른 기능적 평가에서도 유의한 개선이 관찰되었습니다. 치료는 새로운 안전성 신호 없이 우호적인 안전성 프로파일을 보였으나, 41명의 환자에서 치료 관련 이상반응이 보고되었습니다.
이 데이터는 현재 효소 대체요법(ERT)으로 개선되지 않는 LOPD 환자에서 Pombiliti + Opfolda의 지속성 및 효능을 뒷받침합니다.
Amicus Therapeutics (Nasdaq: FOLD) a présenté de nouvelles données à 4 ans de l'étude d'extension en ouvert PROPEL sur Pombiliti® + Opfolda® chez des adultes atteints de la maladie de Pompe à début tardif (LOPD). L'analyse portait sur 82 patients, dont 62 ayant déjà reçu une thérapie de remplacement enzymatique (ERT) et 20 naïfs de l'ERT.
Les résultats clés chez les patients ayant une expérience de l'ERT après 208 semaines ont montré des améliorations sur plusieurs paramètres : +2,3% sur la distance au test de marche de six minutes, +1,6 point au score du test manuel de la force des membres inférieurs, ainsi que des améliorations notables d'autres mesures fonctionnelles. Le traitement a présenté un profil d'innocuité favorable sans nouveaux signaux de sécurité identifiés, bien que 41 patients aient présenté des événements indésirables liés au traitement.
Ces données soutiennent la durabilité et l'efficacité de Pombiliti + Opfolda chez les patients LOPD qui ne s'améliorent pas sous la thérapie de remplacement enzymatique (ERT) actuelle.
Amicus Therapeutics (Nasdaq: FOLD) präsentierte neue 4‑Jahres‑Daten aus der offenen Verlängerungsstudie PROPEL zu Pombiliti® + Opfolda® bei Erwachsenen mit spätmanifestierter Pompe‑Krankheit (LOPD). Die Analyse umfasste 82 Patienten, davon 62 bereits mit ERT behandelt und 20 ERT‑naive.
Wesentliche Befunde bei ERT‑erfahrenen Patienten nach 208 Wochen zeigten Verbesserungen in mehreren Messgrößen: +2,3% beim 6‑Minuten‑Gehstreckentest, +1,6 Punkte beim manuellen Muskeltest der unteren Extremitäten sowie deutliche Verbesserungen in weiteren funktionellen Parametern. Die Behandlung wies ein günstiges Sicherheitsprofil ohne neue Sicherheitsbedenken auf, wobei jedoch 41 Patienten behandlungsbedingte unerwünschte Ereignisse hatten.
Die Daten untermauern die Langzeitwirkung und Wirksamkeit von Pombiliti + Opfolda bei LOPD‑Patienten, die auf die bisherige Enzymersatztherapie (ERT) nicht ansprechen.
- Sustained improvements in muscle function and strength over 4 years
- Multiple positive efficacy measures including +2.3% in walk distance and +1.6 points in muscle test score
- High study completion rate with >95% of patients completing the PROPEL study
- Favorable long-term safety profile with no new safety signals
- 41 patients experienced treatment-related adverse events
- 4 patients discontinued treatment due to adverse events
- 2 patients experienced serious treatment-related adverse events leading to discontinuation
- One patient death reported (though unrelated to treatment)
Insights
Amicus' 4-year Pombiliti+Opfolda data shows sustained benefits in ERT-experienced Pompe patients, bolstering its clinical profile and competitive positioning.
The new 4-year data from Amicus Therapeutics' PROPEL open-label extension study provides compelling evidence of durability for their two-component therapy in late-onset Pompe disease (LOPD). For the ERT-experienced cohort of patients who had been on prior therapy for a median of 7.5 years, the results demonstrate either improvement or stabilization across all key endpoints over 208 weeks - a remarkable achievement considering LOPD's progressive nature.
The stability in six-minute walk distance (+2.3%) and manual muscle test scores (+1.6 points) is particularly significant. In LOPD, natural disease progression typically shows declining ambulatory function and muscle strength over time. The biomarker improvements, including reduced creatine kinase (-160.0 serum CK) and hexose tetrasaccharide (-1.9 mmol/mol creatinine), further confirm sustained reduction in disease activity.
The safety profile remains consistent with previous reports, with 41 patients experiencing treatment-related adverse events leading to only 4 discontinuations over 4 years - a reasonable discontinuation rate for a chronic therapy. These findings are especially meaningful because they address the critical question of long-term efficacy in patients who were not adequately responding to their previous ERT therapy - precisely the population for which Pombiliti+Opfolda is approved in the US.
The additional presentations at ICIEM, particularly the real-world switching study from UK researchers, provide independent validation supporting the clinical benefits observed in the company-sponsored trials. This growing body of evidence strengthens Amicus' position in competing for the ERT-experienced patient population where improvement on current therapy has plateaued.
Long-Term Data Adds to the Growing Body of Evidence Supporting the Compelling Clinical Profile of Pombiliti® + Opfolda®
PRINCETON, N.J., Sept. 08, 2025 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq: FOLD), today announced the presentation of new 4-year muscle function, muscle strength and biomarker endpoints from the PROPEL open-label extension (OLE) study of cipaglucosidase alfa-atga + miglustat (cipa+mig) in adults with late-onset Pompe disease (LOPD) at the International Congress of Inborn Errors of Metabolism (ICIEM) in Kyoto, Japan.
The new analysis, “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,” was conducted on the 82 patients (62 ERT-experienced and 20 ERT-naïve) who were randomized to cipa+mig in PROPEL and who enrolled in the open label extension (OLE).
Pombiliti + Opfolda is indicated in the U.S. for the treatment of adult patients with LOPD weighing ≥40 kg and who are not improving on their current ERT. In the U.S., Pombiliti + Opfolda is not indicated for patients naïve to ERT treatment. The data summarized below are from the ERT-experienced group in the OLE. Pulmonary function data from the PROPEL OLE will be presented separately at an upcoming conference.
The mean age was 48.8 years and the median duration of prior ERT in the ERT-experienced cohort at PROPEL baseline was 7.5 years. In the ERT-experienced group, the measures of muscle function, muscle strength and biomarkers improved and/or were sustained out to 208 weeks. Mean change from PROPEL baseline to week 208 were as follows:
- Percent predicted six-minute walk distance (6MWD), +
2.3% ; - Lower extremity manual muscle test (MMT) score, +1.6 points;
- Gait-Stairs-Gowers-Chair (GSGC) score, +0.1 points;
- PROMIS® physical function score, +1.2 points;
- Serum creatine kinase (CK) levels, -160.0 serum CK; and,
- Urine hexose tetrasaccharide (Hex4), -1.9 mmol/mol creatinine.
No new safety signals were identified. Up to week 208, 41 patients experienced treatment-related treatment-emergent adverse events (TEAEs), leading to four cipa+mig discontinuations, and two patients experienced serious treatment-related TEAEs, leading to two cipa+mig discontinuations. One patient experienced a TEAE (worsening of Lewy body disease) unrelated to study treatment, which led to death; the patient had discontinued from the study prior to death.
“Durability of effect is important for evaluating the impact of treatments for individuals with LOPD. In this new analysis assessing the long-term outcomes from the open label extension of PROPEL, the improvements in muscle function, muscle strength, and biomarkers observed in patients receiving Pombiliti and Opfolda were maintained for four years,” said Priya Kishnani, MD, Chief, Division of Medical Genetics, Chen Family Distinguished Professor of Pediatrics, Chief, Division of Medical Genetics, Duke University Medical Center.
“This new analysis adds to the growing body of evidence supporting the compelling clinical profile of Pombiliti and Opfolda in ERT-experienced adults,” said Jeff Castelli, PhD, Chief Development Officer, Amicus Therapeutics, Inc. “To observe these sustained improvements and stability in the patients in the open label extension at four years is very encouraging given the progressive nature of LOPD. We look forward to presenting long-term extension data across pulmonary 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.”
Other abstracts at ICIEM
In addition to this analysis, the following abstracts related to Pombiliti + Opfolda based on Amicus studies were also presented at ICIEM:
Abstract Title: Cipaglucosidase alfa and alglucosidase alfa enzymes have similar stability at neutral pH and can be stabilized with miglustat
- Presenter: Filip Cosmanescu, Amicus Therapeutics Inc., Princeton, NJ, U.S.A.
Abstract Title: Integrating clinical evidence on cipaglucosidase alfa plus miglustat and alglucosidase alfa via a multi-level network meta-regression
- Presenter: William Kerr, Amicus Therapeutics Ltd, Marlow, U.K.
Abstract Title: PROPEL Japan subpopulation: efficacy and safety of cipaglucosidase alfa plus miglustat versus alglucosidase alfa in patients with late-onset Pompe disease
- Presenter: Hiroshi Kobayashi, The Jikei University School of Medicine, Tokyo, Japan
Abstract Title: ATB200-19: an open-label, expanded access study of the safety and effectiveness of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease in Japan
- Presenter: Aya Narita, ISEIKAI International General Hospital, Osaka, Japan
Abstract Title: PROPEL Australia subpopulation: efficacy and safety of cipaglucosidase alfa plus miglustat versus alglucosidase alfa in patients with late-onset Pompe disease
- Presenter: Michel Tchan, Westmead Hospital, Westmead, NSW, Australia
The following abstract related to Pombiliti + Opfolda from a non-Amicus study was also presented at ICIEM:
Abstract Title: Real World Study: Assessing the impact of switching from alpha-glucosidase to cipaglucosidase alfa with miglustat on disease progression in adults with Pompe disease
- Lead author: Sara Lucas Del Pozo, National Hospital for Neurology and Neurosurgery, UCLH, London, U.K.
- Presenter: Robin Lachmann, National Hospital for Neurology and Neurosurgery, UCLH, London, U.K.
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,
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 (
About the PROPEL Open-label Extension Study
The Phase 3 open-label extension (OLE) study (ATB200-07) is a multicenter, international study designed to evaluate the long-term safety and efficacy of cipaglucosidase alfa-atga + miglustat in adult subjects with LOPD who completed the Phase 3 PROPEL Study (ATB200-03). Of the 118 patients treated in the OLE, 81 continued cipa+mig treatment from PROPEL (cipa+mig group; 61 ERT-experienced prior to PROPEL; 20 ERT-naïve) and 37 switched from alg+pbo to cipa+mig (switch group; 29 ERT-experienced; 8 ERT-naive).
Efficacy endpoints of the study included primary endpoint of change from PROPEL baseline to approximately 4 years in 6-minute walk distance (6MWD), forced vital capacity (FVC), creatine kinase (CK) and hexose tetrasaccharide (Hex4) levels, patient-reported outcomes and safety.
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 ≥
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:
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Vice President, Corporate Communications
dmoore@amicusrx.com
(609) 662-5079
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