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)
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; ATB200-07 Study Group [Collaborative Organization]; Sebok, Agnes [Collaborator]; Pestronk, Alan [Collaborator]; Dominovic-Kovacevic, Aleksandra [Collaborator]; Khan, Aneal [Collaborator]; Koritnik, Blaž [Collaborator]; Tard, Celine [Collaborator]; Lindberg, Christopher [Collaborator]; Quinn, Colin [Collaborator]; Eldridge, Crystal [Collaborator]; Bodkin, Cynthia [Collaborator]; Reyes-Leiva, David [Collaborator]; Hughes, Derralynn [Collaborator]; Stefanescu, Ela [Collaborator]; Salort-Campana, Emmanuelle [Collaborator]; Butler, Ernest [Collaborator]; Bouhour, Francoise [Collaborator]; Kim, Gee [Collaborator]; Papadimas, George Konstantinos [Collaborator]; Parenti, Giancarlo [Collaborator]; Bartosik-Psujek, Halina [Collaborator]; Kushlaf, Hani [Collaborator]; Akihiro, Hashiguchi [Collaborator]; Lau, Heather [Collaborator]; Pedro, Helio [Collaborator]; Andersen, Henning [Collaborator]; Amartino, Hernan [Collaborator]; Shiraishi, Hideaki [Collaborator]; Kobayashi, Hiroshi [Collaborator]; Tarnev, Ivaylo [Collaborator]; Vengoechea, Jaime [Collaborator]; Avelar, Jennifer [Collaborator]; Shin, Jin-Hong [Collaborator]; Nevin, John [Collaborator]; Cauci, Jonathan [Collaborator]; Alonso-Pérez, Jorge [Collaborator]; Janszky, Jozsef [Janszky, József Vladimír (Neurológia), Collaborator] Medical School
(UP); Berthy, Julie [Collaborator]; Kornblum, Cornelia [Collaborator]; Gutschmidt, Kristina [Collaborator]; Molnar, Maria Judit [Molnár, Mária Judit (Neurológia), Collaborator] Genomic Medicine
and the Institute of Rare Dise... (SU / FM / I); Wencel, Marie [Collaborator]; Tarnopolsky, Mark [Collaborator]; Boentert, Matthias [Collaborator]; Tchan, Michel [Collaborator]; Freimer, Miriam [Collaborator]; Longo, Nicola [Collaborator]; Abreu, Nicolas [Collaborator]; Vidal-Fernandez, Nuria [Collaborator]; Musumeci, Olimpia [Collaborator]; Goker-Alpan, Ozlem [Collaborator]; Deegan, Patrick [Collaborator]; Clemens, Paula R [Collaborator]; Roxburgh, Richard [Collaborator]; Henderson, Robert [Collaborator]; Hopkin, Robert [Collaborator]; Sacconi, Sabrina [Collaborator]; Fecarotta, Simona [Collaborator]; Attarian, Shahram [Collaborator]; Wenninger, Stephan [Collaborator]; Dearmey, Stephanie [Collaborator]; Hiwot, Tarekegn [Collaborator]; Burrow, Thomas [Collaborator]; Ruck, Tobias [Collaborator]; Sawada, Tomo [Collaborator]; Laszlo, Vescei [Collaborator]; Löscher, Wolfgang [Collaborator]; Chien, Yin-Hsiu [Collaborator]
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.
