Switching treatment to cipaglucosidase alfa+miglustat positively affects motor function and quality of life in patients with late-onset Pompe disease


Clinical Trials

Poster Number: M230


Barry J Byrne, MD, PhD, University of Florida, Kristl G. Claeys, MD, PhD, Department of Neurology, University Hospitals Leuven; Department of Neuroscience, KU Leuven, Belgium, Paula Clemens, MD, University of Pittsburgh, Jordi Diaz-Manera, MD, PhD, John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle-Upon-Tyne, UK, Mazen Dimachkie, MD, University of Kansas Medical Center, Priya S. Kishnani, MD, Duke University Medical Center, Durham, NC, USA, Hani Kushlaf, MD, University of Cincinnati, Cincinnati, OH, USA, Tahseen Mozaffar, MD, UCI Health, Mark Roberts, MD, PhD, Salford Royal NHS Foundation Trust, Salford, UK, Antonio Toscano, MD, PhD, ERN-NMD Center for Neuromuscular Disorders, University of Messina, Italy, Noemi Hummel, PhD, Certara GmbH, Lörrach, Germany, Mitchell Goldman, MD, PhD, Amicus Therapeutics, Inc., Princeton, NJ, USA, Fred Holdbrook, PhD, Amicus Therapeutics, Inc., Princeton, NJ, USA, Simon Shohet, PhD, Amicus Therapeutics Ltd, Marlow, UK, Benedikt Schoser, MD, PhD, Friedrich-Baur-Institute, Dep. of Neurology LMU Clinics, Ludwig-Maximilians University, Munich

Background: Late-onset Pompe disease (LOPD) substantially impacts motor function and health-related quality of life (HRQoL). The Phase III PROPEL trial (NCT03729362) assessed efficacy and safety of the novel, two-component therapy cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in adults with LOPD.

Objectives: This study aimed to evaluate the impact of switching to cipa+mig on motor function and HRQoL in the prespecified population of enzyme replacement therapy (ERT)-experienced patients in PROPEL.

Methods: PROPEL included assessments of motor function (6-minute walk test; Gait, Stairs, Gowers’ maneuver, and Chair) and patient-reported outcomes (PROs: EQ-5D-5L; Rasch-built Pompe-specific Activity; Subject Global Impression of Change [SGIC]; Patient-Reported Outcomes Measurement Information System [PROMIS]). Group-level analyses estimated between-group differences (least square mean) for motor function and PRO change from baseline to week 52 using analysis of covariance adjusted for baseline age, gender, height, weight, and ERT status. Patient-level responder analyses of PROs compared the proportion of patients satisfying literature-based responder thresholds via chi-square or Fisher’s exact tests.

Results: Group-level analyses favored cipa+mig versus alg+pbo in the vast majority of motor function and PRO measures, with nominal significance for walking tests and SGIC’s “ability to move around” and “energy level”. Patient-level responder analyses showed a greater proportion of patients improved with cipa+mig versus alg+pbo for most PRO measures. Differences in proportions of responders between cipa+mig versus alg+pbo were nominally significant for SGIC’s “overall wellbeing”, “ability to move around”, “muscle function”, and “energy level”.

Conclusions: These analyses highlight the patient perspective and provide evidence that switching from alg+pbo to cipa+mig benefits patients’ motor function and HRQoL. This study was supported by Amicus Therapeutics, Inc.