Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02)

• Published in: Journal of neurology Vol. 271; no. 4; pp. 1787 - 1801
• Main Authors: Byrne, Barry J., Schoser, Benedikt, Kishnani, Priya S., Bratkovic, Drago, Clemens, Paula R., Goker-Alpan, Ozlem, Ming, Xue, Roberts, Mark, Vorgerd, Matthias, Sivakumar, Kumaraswamy, van der Ploeg, Ans T., Goldman, Mitchell, Wright, Jacquelyn, Holdbrook, Fred, Jain, Vipul, Benjamin, Elfrida R., Johnson, Franklin, Das, Sheela Sitaraman, Wasfi, Yasmine, Mozaffar, Tahseen
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2024; Springer Nature B.V
• Subjects: Disease; Enzymes; Hospitals; Immunogenicity; Medicine; Medicine & Public Health; Musculoskeletal system; NCT; NCT02675465; Neurology; Neuroradiology; Neurosciences; Original Communication; Pharmacodynamics; Pharmacokinetics; Safety; Butyldeoxynojirimycin; Lysosomal storage diseases; Glycogen storage disease type II; Pharmacokinetics; Myozyme; Alpha glucosidases; n-Butyldeoxynojirimycin
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-023-12096-0

Cipaglucosidase alfa plus miglustat (cipa + mig) is a novel, two-component therapy for Pompe disease. We report data from the Phase I/II ATB200-02 study for up to 48 months of treatment. Four adult cohorts, including one non-ambulatory ERT-experienced (
n
 = 6) and three ambulatory cohorts, (two enzyme replacement therapy [ERT]-experienced cohorts [2–6 years (
n
 = 11) and ≥ 7 years (
n
 = 6)]), one ERT-naïve cohort (
n
 = 6), received 20 mg/kg intravenous-infused cipa plus 260 mg oral mig biweekly. Change from baseline (CFBL) for multiple efficacy endpoints at 12, 24, 36, and 48 months, pharmacodynamics, pharmacokinetics, safety, and immunogenicity data were assessed. Six-minute walking distance (% predicted) improved at 12, 24, 36, and 48 months: pooled ambulatory ERT-experienced cohorts, mean(± standard deviation [SD]) CFBL: 6.1(± 7.84),
n
 = 16; 5.4(± 10.56),
n
 = 13; 3.4(± 14.66),
n
 = 12; 5.9(± 17.36),
n
 = 9, respectively; ERT-naïve cohort: 10.7(± 3.93),
n
 = 6; 11.0(± 5.06),
n
 = 6; 9.0(± 7.98),
n
 = 5; 11.7(± 7.69),
n
 = 4, respectively. Percent predicted forced vital capacity was generally stable in ERT-experienced cohorts, mean(± SD) CFBL − 1.2(± 5.95),
n
 = 16; 1.0(± 7.96),
n
 = 13; − 0.3(± 6.68),
n
 = 10; 1.0(± 6.42),
n
 = 6, respectively, and improved in the ERT-naïve cohort: 3.2(± 8.42),
n
 = 6; 4.7(± 5.09),
n
 = 6; 6.2(± 3.35),
n
 = 5; 8.3(± 4.50),
n
 = 4, respectively. Over 48 months, CK and Hex4 biomarkers improved in ambulatory cohorts. Overall, cipa + mig was well tolerated with a safety profile like alglucosidase alfa. ATB200-02 results show the potential benefits of cipa + mig as a long-term treatment option for Pompe disease.
Trial registration number
: NCT02675465 January 26, 2016.