Switching treatment to cipaglucosidase alfa plus miglustat positively affects patient-reported outcome measures in patients with late-onset Pompe disease
Authors: Kishnani Priya S. , Byrne Barry J. , Claeys Kristl G. , Díaz-Manera Jordi , Dimachkie Mazen M. , Kushlaf Hani , Mozaffar Tahseen , Roberts Mark , Schoser Benedikt , Hummel Noemi , Kopiec Agnieszka , Holdbrook Fred , Shohet Simon , Toscano Antonio ,   on behalf of the PROPEL Study Group, Sebok Agnes , Pestronk Alan , Dominovic-Kovacevic Aleksandra , Khan Aneal , Koritnik Blaž , Tard Celine , Lindberg Christopher , Quinn Colin , Eldridge Crystal , Bodkin Cynthia , Reyes-Leiva David , Hughes Derralynn , Stefanescu Ela , Salort-Campana Emmanuelle , Butler Ernest , Bouhour Francoise , Kim Gee , Papadimas George Konstantinos , Parenti Giancarlo , Bartosik-Psujek Halina , Akihiro Hashiguchi , Lau Heather , Pedro Helio , Andersen Henning , Amartino Hernan , Shiraishi Hideaki , Kobayashi Hiroshi , Tarnev Ivaylo , Vengoechea Jaime , Avelar Jennifer , Shin Jin-Hong , Cauci Jonathan , Alonso-Pérez Jorge , Janszky Jozsef , Berthy Julie , Kornblum Cornelia , Gutschmidt Kristina , Molnar Maria Judit , Wencel Marie , Tarnopolsky Mark , Tchan Michel , Freimer Miriam , Longo Nicola , Vidal-Fernandez Nuria , Musumeci Olimpia , Goker-Alpan Ozlem , Deegan Patrick , Clemens Paula R , Roxburgh Richard , Henderson Robert , Hopkin Robert , Sacconi Sabrina , Fecarotta Simona , Attarian Shahram , Wenninger Stephan , Dearmey Stephanie , Hiwot Tarekegn , Burrow Thomas , Ruck Tobias , Sawada Tomo , Laszlo Vescei , Löscher Wolfgang , Chien Yin-Hsiu 
Published: November 2024

Abstract
Background
Late-onset Pompe disease (LOPD), a rare autosomal recessive multisystemic disorder, substantially impacts patients’ day-to-day activities, outcomes, and health-related quality of life (HRQoL). The PROPEL trial compared cipaglucosidase alfa plus miglustat (cipa+mig) with alglucosidase alfa plus placebo (alg+pbo) in adult patients with LOPD over 52 weeks and showed improved motor and respiratory function in patients switching treatment from standard-of-care enzyme replacement therapy (ERT) to cipa+mig at baseline. This study evaluated the impact of cipa+mig on patient-reported outcomes (PROs), including HRQoL in ERT-experienced patients, using data from PROPEL.

Methods
PROs evaluated included the Subject’s Global Impression of Change (SGIC), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 20a, PROMIS Fatigue Short Form 8a, Rasch-built Pompe-specific Activity (R-PAct), and European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L). The proportions of responders in the cipa+mig arm and the alg+pbo arm were compared via chi-squared or Fisher’s exact test (patient-level responder analysis), and least squares (LS) mean differences were calculated for change from baseline at Week 52 of the PRO measures (group-level analysis).

Results
At Week 52, patient-level SGIC responder and group-level SGIC analyses favored cipa+mig compared with alg+pbo across all SGIC domains (e.g. 90 vs. 59% responders in the cipa+mig vs. the alg+pbo group for SGIC ability to move around; P = 0.0005; and LS mean difference 0.385; P = 0.02). Similarly, PROMIS Physical Function and Fatigue domains numerically favored cipa+mig in both analyses (e.g. 50 vs. 40% responders in the cipa+mig vs. alg+pbo arm for PROMIS Physical Function; P = 0.37; and LS mean difference 3.1; P = 0.11). R-PAct for both treatment groups was similar in the patient-level responder analysis, but numerically favored alg+pbo in the group-level analysis (35% responders in both arms; P = 0.95; and LS mean difference −0.8; P = 0.48). Self-care, usual activities, and depression/anxiety domains of EQ-5D-5L numerically favored cipa+mig in both analyses (e.g. 20 vs. 12% responders in the cipa+mig vs. alg+pbo arm for EQ-5D-5L self-care; P = 0.54; and LS mean difference −0.108; P = 0.52).

Conclusions
Overall, switching treatment from alglucosidase alfa to cipa+mig positively impacted PRO measurements during the double-blind period of PROPEL.

Trial registration
NCT03729362; Registration date: November 1, 2018; https://clinicaltrials.gov/study/NCT03729362