Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Apr;271(4):1787-1801.
doi: 10.1007/s00415-023-12096-0. Epub 2023 Dec 6.

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)

Barry J Byrne  1 , Benedikt Schoser  2 , Priya S Kishnani  3 , Drago Bratkovic  4 , Paula R Clemens  5 , Ozlem Goker-Alpan  6 , Xue Ming  7   8 , Mark Roberts  9 , Matthias Vorgerd  10 , Kumaraswamy Sivakumar  11 , Ans T van der Ploeg  12 , Mitchell Goldman  13 , Jacquelyn Wright  13 , Fred Holdbrook  13 , Vipul Jain  13 , Elfrida R Benjamin  13 , Franklin Johnson  13 , Sheela Sitaraman Das  13 , Yasmine Wasfi  13 , Tahseen Mozaffar  14
Affiliations
Clinical Trial

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)

Barry J Byrne et al. J Neurol. 2024 Apr.

Erratum in

Abstract

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.

Keywords: n-Butyldeoxynojirimycin; Alpha glucosidases; Glycogen storage disease type II; Lysosomal storage diseases; Myozyme; Pharmacokinetics.

PubMed Disclaimer

Conflict of interest statement

Barry J. Byrne has participated as a consultant/advisory board member for Pfizer, Amicus Therapeutics, Inc., and Sanofi. He also owns stocks in Lacerta Therapeutics. Benedikt Schoser has received unrestricted research grants from Amicus Therapeutics, Inc., Astellas, Roche, Marigold Foundation, and the AMDA Foundation and speaker’s honoraria from Amicus Therapeutics, Inc., Alexion, Kedrion, and Sanofi. He has participated as a scientific advisor for Amicus Therapeutics, Inc., Argenx, Astellas, Maze, Pepgen, Sanofi, Spark, and Taysha. He declares no stocks or shares. Priya S. Kishnani has received research/grant support from Sanofi Genzyme and Amicus Therapeutics, Inc. and has received consulting fees and honoraria from Sanofi Genzyme, Amicus Therapeutics, Inc., Maze Therapeutics, Bayer, and Asklepios Biopharmaceutical, Inc. (AskBio). She is a member of the Pompe and Gaucher Disease Registry Advisory Board for Sanofi Genzyme, the Pompe Disease Advisory Board for Amicus Therapeutics, Inc., and the Advisory Board for Baebies. Priya S. Kishnani has equity with Maze Therapeutics and has held equity in Asklepios Biopharmaceuticals and may receive milestone payments related to that equity in the future. Paula R. Clemens has received grant support from Amicus Therapeutics, Inc., Sanofi Genzyme, Spark, ReveraGen, NS Pharma, MDA, NIH, FDA, and Foundation to Eradicate Duchenne. She received an educational honorarium to speak on Pompe disease by Catalyst Medical Education. She was a consultant for Epirium Bio Inc. Ozlem Goker-Alpan has received consulting fees from Sanofi Genzyme, Amicus Therapeutics, Inc., BioMarin, Sanofi, Shire HGT, and Takeda. She has received grants from Sanofi-Genzyme, Amicus Therapeutics, Inc., Freeline, Genentech, Protalix, Sangamo, Sanofi, and Takeda. Mark Roberts has received fees for advisory boards and speaker honoraria from Sanofi, BioMarin, and Amicus Therapeutics, Inc. Matthias Vorgerd has received speaker’s honoraria including travel costs from Hormosan-Pharma, Sanofi Genzyme, and Amicus Therapeutics, Inc. Ans T. van der Ploeg is an advisory board member of Amicus Therapeutics, Inc., BioMarin, Sanofi Genzyme, and Spark Therapeutics. She has provided consultancies for Amicus Therapeutics, Inc., BioMarin, Sanofi Genzyme, and Spark Therapeutics and has contracted research for Amicus Therapeutics, Inc., BioMarin, Sanofi Genzyme, and Spark Therapeutics. All collaborations are done under an agreement between Erasmus MC and these industries. Tahseen Mozaffar has participated in an advisory capacity for Abbvie, Alexion, Amicus Therapeutics, Inc., Argenx, Audentes, Maze Therapeutics, Modis, Momenta, Ra Pharmaceuticals, Sanofi Genzyme, Sarepta, Spark Therapeutics, UCB, and Ultragenyx, and has participated in the speaker’s bureau for Sanofi Genzyme. He is a member of the medical advisory board for the Myositis Association, Neuromuscular Disease Foundation, Myasthenia Gravis Foundation of California, and Myasthenia Gravis Foundation of America. He has received research funding from the Myositis Association, the Muscular Dystrophy Association, the NIH, and from the following sponsors: Alexion, Amicus Therapeutics, Inc., Argenx, Audentes, Bristol-Myers Squib, Cartesian Therapeutics, Grifols, Momenta, Ra Pharmaceuticals, Sanofi Genzyme, Spark Therapeutics, UCB, and Valerion. He is a member of the Data safety monitoring board for Acceleron, Avexis, Sarepta, and the NIH. Mitchell Goldman, Jacquelyn Wright, Fred Holdbrook, Vipul Jain, Elfrida Benjamin, Franklin Johnson, Sheela Sitaraman Das, and Yasmine Wasfi are employees of Amicus Therapeutics, Inc. and hold stocks and shares in Amicus Therapeutics, Inc. Drago Bratkovic, Xue Ming, and Kumaraswamy Sivakumar declare no competing interests.

Figures

Fig. 1
Fig. 1
ATB200-02 study design: 18-week primary treatment period with long-term extension. Stage 3 was a 2-year treatment period during which patients received 20 mg/kg of IV-infused cipaglucosidase alfa co-administered with 260 mg of miglustat administered orally every 2 weeks. Stage 4 is an ongoing long-term extension to provide additional safety and efficacy data. aWith 20 mg/kg alglucosidase alfa Q2W; bPK assessments for GAA activity; total GAA protein and miglustat in stage 3 were only performed for the first and third doses for cohort 3. Sparse blood sampling for total GAA protein was performed after ≥ 18 months of treatment in cohorts 1 and 3. If a patient had completed stage 3, sparse PK sampling was performed in stage 4. ERT enzyme replacement therapy, GAA acid α-glucosidase, IV intravenous, PK pharmacokinetics, Q2W every 2 weeks
Fig. 2
Fig. 2
Patient disposition. Cohort 1: ERT experienced (2–6 years), ambulatory; cohort 2: ERT experienced (≥ 2 years), non-ambulatory; cohort 3: ERT naïve, ambulatory (1 patient in cohort 3 received a single dose of alglucosidase alfa before moving to Australia where this treatment is unavailable and was therefore eligible for inclusion in cohort 3); cohort 4: ERT experienced (≥ 7 years), ambulatory. AE adverse event, ERT enzyme replacement therapy
Fig. 3
Fig. 3
CFBL in % predicted 6MWD in ambulatory a ERT-experienced and b ERT-naïve patients. Pooled data from cohorts 1 and 4 for ERT-experienced patients. No applicable data are available for cohort 2 (non-ambulatory patients). 6MWD 6-min walking distance, CFBL change from baseline, ERT enzyme replacement therapy, SD standard deviation, SE standard error
Fig. 4
Fig. 4
CFBL in % predicted FVC in ambulatory a ERT-experienced and b ERT-naïve patients. Pooled data from cohorts 1 and 4 for ERT-experienced patients. aOne patient in the ERT-naïve cohort experienced a large drop in % predicted FVC at month 21, which returned to previous levels at the following visit (month 24). CFBL change from baseline, FVC forced vital capacity, SD standard deviation, SE standard error
Fig. 5
Fig. 5
Absolute CFBL in MMT lower extremity score in ambulatory a ERT-experienced and b ERT-naïve patients. Pooled data from cohorts 1 and 4 for ERT-experienced patients. No applicable data are available for cohort 2 (non-ambulatory patients). CFBL change from baseline, ERT enzyme replacement therapy, MMT manual muscle test, SD standard deviation, SE standard error
Fig. 6
Fig. 6
Percentage CFBL in a serum CK and b urine Hex4 in ambulatory patients over 48 months. Pooled data from cohorts 1, and 4 for ERT-experienced patients. aLower normal CK limit = 26 IU/L, upper normal CK limit = 192 IU/L. CFBL change from baseline, CK serum creatine kinase, ERT enzyme replacement therapy, Hex4 urine glucose tetrasaccharide, SD standard deviation, SE standard error
See this image and copyright information in PMC

References

    1. Cabello J, Marsden D (2017) Pompe disease: clinical perspectives. Orphan Drugs: Res Rev 7:1–10
    1. Niño MY, in’t Groen SLM, Bergsma AJ et al (2019) Extension of the Pompe mutation database by linking disease-associated variants to clinical severity. Hum Mutat 40:1954–1967 - PMC - PubMed
    1. Cupler EJ, Berger KI, Leshner RT et al (2012) Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve 45:319–333 - PMC - PubMed
    1. American Association of Neuromuscular Electrodiagnostic Medicine (2009) Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle Nerve 40:149–160 - PubMed
    1. Kishnani PS, Howell RR (2004) Pompe disease in infants and children. J Pediatr 144:S35-43 - PubMed

Publication types

Associated data