Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Tina Duong¹, Priya S Kishnani², Kristina An Haack³, Meredith C Foster⁴, James B Gibson⁵, Catherine Wilson⁴, Si Houn Hahn⁶, Richard Hillman⁷, David Kronn⁸, Nancy D Leslie⁹, Loren D M Peña^{2

10

11}, Susan E Sparks⁴, David W Stockton¹², Pranoot Tanpaiboon^{13

14}, John W Day¹; Pompe ADVANCE Study Consortium

Affiliations

¹ Department of Neurology, Division of Neuromuscular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
² Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
³ Sanofi, Chilly-Mazarin, France.
⁴ Sanofi, Cambridge, MA, USA.
⁵ Clinical and Metabolic Genetics, Dell Children's Medical Group, Austin, TX, USA.
⁶ Departments of Pediatrics and Medicine and Biochemical Genetics Program, Seattle Children's Hospital/University of Washington, Seattle, WA, USA.
⁷ University of Missouri Child Health, Columbia, MO, USA.
⁸ Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY, USA.
⁹ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹⁰ Current address: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹¹ Current address: University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹² Division of Genetic, Genomic, and Metabolic Disorders, Central Michigan University and Children's Hospital of Michigan, Detroit, MI, USA.
¹³ Rare Disease Institute, Children's National Hospital, Washington, DC, USA.
¹⁴ Current address: Division of Medical Genetics, Child Health Research Center, Torrance, CA, USA.

PMID: 36214004
PMCID: PMC9697057
DOI: 10.3233/JND-210784

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Tina Duong et al. J Neuromuscul Dis. 2022.

. 2022;9(6):713-730.

doi: 10.3233/JND-210784.

Authors

Affiliations

¹ Department of Neurology, Division of Neuromuscular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
² Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
³ Sanofi, Chilly-Mazarin, France.
⁴ Sanofi, Cambridge, MA, USA.
⁵ Clinical and Metabolic Genetics, Dell Children's Medical Group, Austin, TX, USA.
⁶ Departments of Pediatrics and Medicine and Biochemical Genetics Program, Seattle Children's Hospital/University of Washington, Seattle, WA, USA.
⁷ University of Missouri Child Health, Columbia, MO, USA.
⁸ Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY, USA.
⁹ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹⁰ Current address: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹¹ Current address: University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹² Division of Genetic, Genomic, and Metabolic Disorders, Central Michigan University and Children's Hospital of Michigan, Detroit, MI, USA.
¹³ Rare Disease Institute, Children's National Hospital, Washington, DC, USA.
¹⁴ Current address: Division of Medical Genetics, Child Health Research Center, Torrance, CA, USA.

PMID: 36214004
PMCID: PMC9697057
DOI: 10.3233/JND-210784

Abstract

Background: ADVANCE (NCT01526785) presented an opportunity to obtain a more nuanced understanding of motor function changes in treatment-experienced children with Pompe disease receiving 4000L-production-scale alglucosidase alfa for 52 weeks.

Objective: To estimate minimal detectable change (MDC) and effect size on Gross Motor Function Measure-88 (GMFM-88) after 52 weeks of 4000L alglucosidase alfa (complete data N = 90).

Methods: The GMFM-88 mean total % score changes, MDC, and effect size were analyzed post hoc by Pompe Motor Function Level at enrollment, age groups at enrollment, and fraction of life on pre-study 160L-production-scale alglucosidase alfa.

Results: Overall, participants aged < 2 years surpassed MDC at Week 52 (change [mean±standard deviation] 21.1±14.1, MDC range 5.7-13.3, effect size 1.1), whereas participants aged≥2 years did not attain this (change -0.9±15.3, MDC range 10.8-25.2, effect size -0.03). In participants aged < 2 years, improvements surpassed the MDC for walkers (change 17.1±13.3, MDC range 3.0-6.9, effect size 1.7), supported standers (change 35.2±18.0, MDC range 5.9-13.7, effect size 1.8) and sitters (change 24.1±12.1, MDC range 2.6-6.2, effect size 2.7). Age-independent MDC ranges were only attained by walkers (change 7.7±12.3, MDC range 6.4-15.0, effect size 0.4) and sitters (change 9.9±17.2, MDC range 3.3-7.7, effect size 0.9).

Conclusions: These first GMFM-88 minimal-detectable-change estimates for alglucosidase alfa-treated Pompe disease offer utility for monitoring motor skills.

Trial registration: ClinicalTrials.gov; NCT01526785; Registered 6 February 2012; https://clinicaltrials.gov/ct2/show/NCT01526785.

Keywords: Alglucosidase alfa; Gross Motor Function Classification System; Gross Motor Function Measure-88; Pompe Motor Function History; infantile-onset Pompe disease; late-onset Pompe disease; minimal detectable change.

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Conflict of interest statement

TD reports Pompe-disease-related honoraria from Sanofi (advisory boards within and outside the scope of the study), membership of advisory boards for Roche, Scholar Rock, Cure SMA, Cytokinetics, Biogen, Novartis, Bristol Myers Squibb, and SMA Foundation, and service as a consultant for Roche, Audentes, Bristol Myers Squibb, Novartis, Trinds, ATOM International, and Scholar Rock. PSK reports grants from Amicus Therapeutics, Sanofi, and Valerion Therapeutics; consulting fees and honoraria from Amicus Therapeutics, Asklepios BioPharmaceuticals (AskBio), and Sanofi; membership of the Pompe and Gaucher Disease Registry Advisory Boards for Amicus Therapeutics, Baebies, and Sanofi; and equity with Asklepios BioPharmaceuticals (AskBio). JBG discloses study sponsorship and professional writing assistance from Sanofi during the conduct of the study and advisory board membership for Mallinckrodt Pharmaceuticals outside the submitted work. SHH reports personal fees from Alexion, employment by Seattle Children’s Hospital, and personal fees and grants from Sanofi outside the submitted work. RH has nothing to disclose. DK reports research funding from Sanofi and New York Medical College during the conduct of the study and is on the Sanofi speakers’ bureau for Pompe disease. NDL reports personal fees (honoraria for advisory board activities) and non-financial support (professional writing support) from Sanofi during the conduct of the study and outside the submitted work. LDMP discloses grant support and advisory board membership for AveXis, grant support from Biogen, Ionis, and Sanofi, advisory board membership for Roche/Genentech, and research support from Roivant, Inc. DWS is a member of the Sanofi Pompe Registry Advisory Board outside the submitted work and discloses grant support from Sanofi during the conduct of the study. PT discloses current employment by Quest Diagnostics. KAH, SS, and MCF disclose being employees of Sanofi and may hold stock and/or stock options in the company; CW discloses a contract with Sanofi for consulting work during the conduct of the study and services as a consultant for REGENXBIO. JWD reports personal fees from Audentes, grants from Ionis Pharmaceuticals, and grants and personal fees from AveXis, Biogen, Cytokinetics, Roche/Genentech, Sarepta, and Scholar Rock, outside the submitted work; he also has a patent 7442782 with royalties paid to Athena Diagnostics.

Figures

**Fig. 1**
Percentages of participants with positive, none, or negative GMFM-88 dimension scores change after 52 weeks. Percentages of participants (who had Week 52 data) with positive change, no change, or negative change in GMFM-88 dimension scores after 52 weeks of 4000L alglucosidase alfa, by age and Pompe Motor Function Level. Pompe Motor Function Level was available for 89 of the 90 participants who had GMFM-88 data available at enrollment and Week 52. In the younger cohort there were no Level II (supported walkers).

See this image and copyright information in PMC

References

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Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Affiliations

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical