Long-term efficacy and safety of cipaglucosidase alfa/miglustat in patients with Pompe disease: a Phase III open-label extension study (ATB200-07)

Topic:

Clinical Trials

Poster Number: 136

Author(s):

Tahseen Mozaffar, MD, University of California Irvine, Drago Bratkovic, MD, PARC Research Clinic, Royal Adelaide Hospital, Adelaide, SA, Australia, Barry Byrne, MD, PhD, University of Florida, Jordi Díaz-Manera, MD, PhD, John Walton Muscular Dystrophy Research Centre, Newcastle Upon Tyne, UK, Pascal Laforêt, MD, PhD, Nord-Est/Ile-de-France Neuromuscular Reference Center, Raymond-Poincaré Hospital, Garches, France, Priya S. Kishnani, MD, Duke University Medical Center, Durham, NC, USA, Mark Robert, MD, Salford Royal NHS Foundation Trust, Salford, UK, Antonio Toscano, MD, Reference Center for Rare Neuromuscular Disorders, University of Messina, Messina, Italy, Ans T. van der Ploeg, MD, PhD, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, Jeff Castelli, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Mitchell Goldman, MD, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Hai Jiang, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Sheela Sitaraman Das, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Yasmine Wasfi, MD, PhD, Amicus Therapeutics, Inc., Philadelphia, PA, USA, Benedikt Schoser; on behalf of the COMET Investigator Group, MD, Friedrich-Baur-Institute, Department of Neurology, LMU Klinikum München, München, Germany

Background
The Phase III double-blind PROPEL study (NCT03729362) compared the investigational two component therapy cipaglucosidase alfa/miglustat (cipa/mig) with alglucosidase alfa/placebo (alg/pbo) in adult ambulatory patients with late-onset Pompe disease (LOPD) over 52 weeks. The ongoing open-label extension (OLE) of PROPEL (NCT04138277) evaluates long-term safety and efficacy of cipa/mig.

Methods
Outcomes include 6 minute walk distance (6MWD), forced vital capacity (FVC), creatine kinase (CK) and hexose tetrasaccharide (Hex4) levels and safety. Data are reported as change from the PROPEL baseline to OLE week 52 (104 weeks after the PROPEL baseline).

Results
In the OLE (N=119; 91 enzyme replacement therapy [ERT]-experienced patients and 28 ERT naïve patients), 82/85 (96.5%) patients previously treated with cipa/mig in PROPEL continued cipa/mig, and 37/38 (97.4%) switched from alg/pbo to cipa/mig; 90.8% of patients remained in the OLE through week 52. Mean change in % predicted 6MWD was +3.1 (8.07 standard deviation) for cipa/mig–cipa/mig and −0.5 (7.76) for alg/pbo–cipa/mig in ERT-experienced patients, and +8.6 (8.57) for cipa/mig–cipa/mig and +8.9 (11.65) for alg/pbo–cipa/mig in ERT-naïve patients. Mean change in % predicted FVC was −0.6 (7.50) for cipa/mig–cipa/mig and −3.8 (6.23) for alg/pbo–cipa/mig in ERT-experienced patients, and −4.8 (6.48) and −3.1 (6.66) in ERT naïve patients. Mean reduction in CK (U/L) for ERT-experienced and ERT-naïve patients was −132.1 (215.74) and −216.9 (243.66) for cipa/mig–cipa/mig and −161.0 (269.52) and −218.6 (316.47) for alg/pbo–cipa/mig, respectively. Mean reduction in Hex4 (mmol/mol) for ERT-experienced and ERT-naïve patients was −1.9 (3.22) and −2.9 (2.45) for cipa/mig–cipa/mig and −2.6 (3.75) and −2.9 (2.22) for alg/pbo–cipa/mig, respectively. During PROPEL and through week 52 of the OLE, treatment-emergent adverse events occurred in 84 (98.8%) cipa/mig–cipa/mig and 36 (97.3%) alg/pbo–cipa/mig patients. During the OLE, three patients discontinued because of infusion-associated reactions (urticaria, urticaria and hypotension, and anaphylaxis) and no new safety signals were identified.

Conclusions
Data demonstrate treatment with cipa/mig up to 104 weeks was associated with a durable effect and was well tolerated, supporting long-term benefits of treatment for patients with LOPD.
Supported by Amicus Therapeutics, Inc.