104-week efficacy and safety of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease: a phase III open-label extension study (ATB200-07)

• DOI: 10.1007/s00415-024-12236-0
• Publication Date: 2024-02-28T19:02:37Z
• Authors: Benedikt Schoser; Priya S. Kishnani; Drago Bratkovic; Barry J. Byrne; Kristl G. Claeys; Jordi Díaz-Manera; Pascal Laforêt; Mark Roberts; Antonio Toscano; Ans T. van der Ploeg; Jeff Castelli; Mitchell Goldman; Fred Holdbrook; Sheela Sitaraman Das; Yasmine Wasfi; Tahseen Mozaffar; ; Agnes Sebok; Alan Pestronk; Aleksandra Domino...; Aneal Khan; Blaž Koritnik; Celine Tard; Christopher Lindberg; Colin Quinn; Crystal Eldridge; Cynthia Bodkin; David Reyes-Leiva; Derralynn Hughes; Ela Stefanescu; Emmanuelle Salort...; Ernest Butler; Francoise Bouhour; Gee Kim; George Konstantin...; Giancarlo Parenti; Halina Bartosik-P...; Hani Kushlaf; Hashiguchi Akihiro; Heather Lau; Helio Pedro; Henning Andersen; Hernan Amartino; Hideaki Shiraishi; Hiroshi Kobayashi; Ivaylo Tarnev; Jaime Vengoechea; Jennifer Avelar; Jin-Hong Shin; John Nevin; Jonathan Cauci; Jorge Alonso-Pérez; Jozsef Janszky; Julie Berthy; Cornelia Kornblum; Kristina Gutschmidt; Maria Judit Molnar; Marie Wencel; Mark Tarnopolsky; Matthias Boentert; Michel Tchan; Miriam Freimer; Nicola Longo; Nicolas Abreu; Nuria Vidal-Ferna...; Olimpia Musumeci; Ozlem Goker-Alpan; Patrick Deegan; Paula R. Clemens; Richard Roxburgh; Robert Henderson; Robert Hopkin; Sabrina Sacconi; Simona Fecarotta; Shahram Attarian; Stephan Wenninger; Stephanie Dearmey; Tarekegn Hiwot; Thomas Burrow; Tobias Ruck; Tomo Sawada; Vescei Laszlo; Wolfgang Löscher; Yin-Hsiu Chien
• Keywords: Male; Adult; 1-Deoxynojirimycin; Clinical Neurology; 610; DIAGNOSIS; Lysosomal storage disorders; ENZYME REPLACEMENT THERAPY; Drug Therapy; Double-Blind Method; Humans; Alpha glucosidase; Enzyme Replacement Therapy; Enzyme Inhibitors; Aged; Science & Technology; Original Communication; Glycogen Storage Disease Type II; 600; alpha-Glucosidases; Middle Aged; Glycogen storage disease type II; Myozyme; Treatment Outcome; n-butyldeoxynojirimycin, Alpha glucosidase, Glycogen storage disease type II, Lysosomal storage disorders, Myozyme; Combination; Female; Drug Therapy, Combination; Neurosciences & Neurology; CONSENSUS; Life Sciences & Biomedicine; n-butyldeoxynojirimycin

Abstract The phase III double-blind PROPEL study compared the novel two-component therapy cipaglucosidase alfa + miglustat (cipa mig) with alglucosidase placebo (alg pbo) in adults late-onset Pompe disease (LOPD). This ongoing open-label extension (OLE; NCT04138277) evaluates long-term safety and efficacy of cipa mig. Outcomes include 6-min walk distance (6MWD), forced vital capacity (FVC), creatine kinase (CK) hexose tetrasaccharide (Hex4) levels, patient-reported outcomes safety. Data are reported as change from baseline to OLE week 52 (104 weeks post-PROPEL baseline). Of 118 patients treated OLE, 81 continued mig treatment group; 61 enzyme replacement [ERT] experienced prior PROPEL; 20 ERT naïve) 37 switched alg pbo (switch 29 experienced; 8 naive). Mean (standard deviation [SD]) % predicted 6MWD 104 was 3.1 (8.1) for − 0.5 (7.8) ERT-experienced switch group, 8.6 (8.6) 8.9 (11.7) ERT-naïve group. (SD) FVC 0.6 (7.5) 3.8 (6.2) 4.8 (6.5) (6.7), respectively, patients. CK Hex4 levels improved both groups by treatment. Three discontinued due infusion-associated reactions. No new signals were identified. Cipa up associated overall maintained improvements (6MWD, biomarkers) or stabilization (FVC) durability, well tolerated, supporting benefits LOPD. Trial registration number : NCT04138277; trial start date: December 18, 2019.