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)
Authors: Schoser Benedikt , Kishnani Priya S. , Bratkovic Drago , Byrne Barry J. , Claeys Kristl G. , Díaz-Manera Jordi , Laforêt Pascal , Roberts Mark , Toscano Antonio , van der Ploeg Ans T. , Castelli Jeff , Goldman Mitchell , Holdbrook Fred , Sitaraman Das Sheela , Wasfi Yasmine , Mozaffar Tahseen ,   the ATB200-07 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 , Kushlaf Hani , Akihiro Hashiguchi , Lau Heather , Pedro Helio , Andersen Henning , Amartino Hernan , Shiraishi Hideaki , Kobayashi Hiroshi , Tarnev Ivaylo , Vengoechea Jaime , Avelar Jennifer , Shin Jin-Hong , Nevin John , Cauci Jonathan , Alonso-Pérez Jorge , Janszky Jozsef , Berthy Julie , Kornblum Cornelia , Gutschmidt Kristina , Molnar Maria Judit , Wencel Marie , Tarnopolsky Mark , Boentert Matthias , Tchan Michel , Freimer Miriam , Longo Nicola , Abreu Nicolas , 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: February 2024

The phase III double-blind PROPEL study compared the novel two-component therapy cipaglucosidase alfa + miglustat (cipa + mig) with alglucosidase alfa + placebo (alg + pbo) in adults with 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) and hexose tetrasaccharide (Hex4) levels, patient-reported outcomes and safety. Data are reported as change from PROPEL baseline to OLE week 52 (104 weeks post-PROPEL baseline). Of 118 patients treated in the OLE, 81 continued cipa + mig treatment from PROPEL (cipa + mig group; 61 enzyme replacement therapy [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). Mean (standard deviation [SD]) change in % predicted 6MWD from baseline to week 104 was + 3.1 (8.1) for cipa + mig and − 0.5 (7.8) for the ERT-experienced switch group, and + 8.6 (8.6) for cipa + mig and + 8.9 (11.7) for the ERT-naïve switch group. Mean (SD) change in % predicted FVC was − 0.6 (7.5) for cipa + mig and − 3.8 (6.2) for the ERT-experienced switch group, and − 4.8 (6.5) and − 3.1 (6.7), respectively, in ERT-naïve patients. CK and Hex4 levels improved in both treatment groups by week 104 with cipa + mig treatment. Three patients discontinued the OLE due to infusion-associated reactions. No new safety signals were identified. Cipa + mig treatment up to 104 weeks was associated with overall maintained improvements (6MWD, biomarkers) or stabilization (FVC) from baseline with continued durability, and was well tolerated, supporting long-term benefits for patients with LOPD.

Trial registration number: NCT04138277; trial start date: December 18, 2019.