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Mol Genet Metab. 2020 Feb;129(2):67-72. doi: 10.1016/j.ymgme.2019.12.008. Epub 2019 Dec 10.

Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease.

Author information

1
Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, United States of America; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, United States of America. Electronic address: dwight.koeberl@duke.edu.
2
Department of Physical and Occupational Therapy, Duke University School of Medicine, Durham, NC 27710, United States of America.
3
Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, United States of America.
4
Division of Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, United States of America.
5
Sanofi Genzyme, Cambridge, MA, USA.
6
Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, United States of America; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, United States of America.

Abstract

This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4) years and with no contraindications to intake of albuterol. Twelve of 13 participants completed the study. No serious adverse events were related to albuterol, and transient minor drug-related adverse events included muscle spasms and tremors. For the albuterol group, forced vital capacity in the supine position increased by 10% (p < .005), and forced expiratory volume in one second increased by 8% (p < .05); the six-minute walk test increased 25 m (p < .05; excluding one participant unable to complete muscle function testing); the Gross Motor Function Measure increased by 8% (p < .005) with the greatest increases in the Standing (18%; p < .05) and Walking, Running, and Jumping (11%; p < .005) subtests. No significant improvements would be expected in patients with late-onset Pompe disease who were stably treated with enzyme replacement therapy. The placebo group demonstrated no significant increases in performance on any measure. These data support a potential benefit of extended-release albuterol as adjunctive therapy in carefully selected patients with late-onset Pompe disease based on ability to take albuterol on enzyme replacement therapy (NCT01885936).

Conflict of interest statement

Declaration of Competing Interest This study was supported in part by grant support in the past from Genzyme Sanofi. Dr. Koeberl is an editor for Genetics in Medicine. He has served on a data and safety monitoring board for Baxter International, Shire, and for Takeda. He has received a grant from Viking Therapeutics and from Sangamo. He received an honorarium and grant support in the past from Genzyme Sanofi. Dr. Case has received honoraria from Genzyme Sanofi, has participated in research supported by Genzyme Sanofi, Valerion, Biomarin, and by Roivant Sciences; and is a member of the Pompe Registry North American Board of Advisors Genzyme Sanofi. Dr. Desai, Dr. Smith, Ms. Walters, and Dr. Han report no relevant disclosures. Dr. Thurberg is an employee of Genzyme Sanofi. Dr. Young has received grant support from Sanofi Genzyme, Amicus Therapeutics, Biomarin Pharmaceutical, PTC Therapeutics, and Valerion Therapeutics and has received consulting fees for Amicus Therapeutics, Sanofi Genzyme, and PTC Therapeutics. Dr. Bali has received research grant support and travel funds from Sanofi Genzyme, Baebies Inc., Biomarin and Alexion, Inc. Dr. Kishnani has received research/grant support from Sanofi Genzyme and Valerion Therapeutics. She received consulting fees and honoraria from Sanofi Genzyme, Amicus Therapeutics, and Vertex. She is a member of the Pompe and Gaucher Disease Registry Advisory Board for Genzyme Sanofi and on the Amicus Scientific Advisory Board. Dr. Koeberl and Dr. Kishnani have developed the technology that is being used in the study. If the technology is commercially successful in the future, the developers and Duke University may benefit financially.

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