A Disease Progression Model Comparing Respiratory and Motor Decline in People With Late-Onset Pompe Disease Treated With Cipaglucosidase Alfa Plus Miglustat vs. Alglucosidase Alfa
Author(s)
Amy Dymond, BSc, MSc1, William Green, BSc, MSc1, Matthew Crabtree, BSc, MPH2, Alasdair MacCulloch, BSc, PhD2, Neil Johnson, BSc2, Simon Shohet, PhD3, Vera Gielen, PhD2, Sophie Clarke, PhD2, Patrick Deegan, MD4, Jordi Diaz-Manera, MD, PhD5.
1York Health Economics Consortium, York, United Kingdom, 2Amicus Therapeutics Ltd, Marlow, United Kingdom, 3Retired from, Amicus Therapeutics Ltd, Marlow, United Kingdom, 4Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom, 5John Walton Muscular Dystrophy Research Centre, Newcastle University & Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom.
1York Health Economics Consortium, York, United Kingdom, 2Amicus Therapeutics Ltd, Marlow, United Kingdom, 3Retired from, Amicus Therapeutics Ltd, Marlow, United Kingdom, 4Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom, 5John Walton Muscular Dystrophy Research Centre, Newcastle University & Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom.
OBJECTIVES: Late-onset Pompe disease (LOPD) is a rare lysosomal disease primarily impacting muscle strength and respiratory function. Patients often require mobility and respiratory support over time despite receiving enzyme replacement therapy (ERT). Given limited studies on lifetime trajectory of people with LOPD treated with ERT, we modelled long-term disease progression for people receiving alglucosidase alfa (alg) or cipaglucosidase alfa + miglustat (cipa+mig).
METHODS: A patient-level simulation model estimated lifetime mobility and respiratory disease progression outcomes among people with LOPD treated with cipa+mig versus alg based on 6-minute walk distance and % predicted forced vital capacity. The model used baseline characteristics and outcome data from PROPEL/PROPEL open-label extension (NCT03729362/NCT04138277) and ATB200-02 (NCT02675465) studies up to 4 years for cipa+mig and 1 year for alg. Thereafter, data from the French Pompe disease registry (Semplicini 2020) were used to project the rate of decline, with a 15% slower rate for cipa+mig than alg. This rate varied in scenarios between 5% (conservative) and 25% (optimistic). Thresholds for intermittent and complete mobility and respiratory support were estimated based on UK clinical opinion. Mortality was based on published rates (Güngör 2013).
RESULTS: The model estimated that people receiving cipa+mig spend an additional 2.72 years requiring no mobility or respiratory support (conservative 2.11, optimistic 3.52) compared with those receiving alg. Additionally, people receiving alg need mobility and respiratory support 3.39 (conservative 2.08, optimistic 4.65) and 2.45 years (conservative 1.87, optimistic 2.92) earlier than those receiving cipa+mig, respectively.
CONCLUSIONS: In this model, cipa+mig delayed disease progression compared with alg in people with LOPD, increasing the time they did not depend on mobility and respiratory support. While data on progression to respiratory and mobility support are limited, this model, informed by clinical and real-world evidence and expert input, suggests potential for cipa+mig to provide quality-of-life benefits for people with LOPD compared with alg.
METHODS: A patient-level simulation model estimated lifetime mobility and respiratory disease progression outcomes among people with LOPD treated with cipa+mig versus alg based on 6-minute walk distance and % predicted forced vital capacity. The model used baseline characteristics and outcome data from PROPEL/PROPEL open-label extension (NCT03729362/NCT04138277) and ATB200-02 (NCT02675465) studies up to 4 years for cipa+mig and 1 year for alg. Thereafter, data from the French Pompe disease registry (Semplicini 2020) were used to project the rate of decline, with a 15% slower rate for cipa+mig than alg. This rate varied in scenarios between 5% (conservative) and 25% (optimistic). Thresholds for intermittent and complete mobility and respiratory support were estimated based on UK clinical opinion. Mortality was based on published rates (Güngör 2013).
RESULTS: The model estimated that people receiving cipa+mig spend an additional 2.72 years requiring no mobility or respiratory support (conservative 2.11, optimistic 3.52) compared with those receiving alg. Additionally, people receiving alg need mobility and respiratory support 3.39 (conservative 2.08, optimistic 4.65) and 2.45 years (conservative 1.87, optimistic 2.92) earlier than those receiving cipa+mig, respectively.
CONCLUSIONS: In this model, cipa+mig delayed disease progression compared with alg in people with LOPD, increasing the time they did not depend on mobility and respiratory support. While data on progression to respiratory and mobility support are limited, this model, informed by clinical and real-world evidence and expert input, suggests potential for cipa+mig to provide quality-of-life benefits for people with LOPD compared with alg.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
MSR2
Topic
Methodological & Statistical Research
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity), Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal), Neurological Disorders, Rare & Orphan Diseases