Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Tina Duong; Priya S Kishnani; Kristina An Haack; Meredith C Foster; James B Gibson; Catherine Wilson; Si Houn Hahn; Richard Hillman; David Kronn; Nancy D Leslie; Loren D M Peña; Susan E Sparks; David W Stockton; Pranoot Tanpaiboon; John W Day; Pompe ADVANCE Study Consortium

doi:10.3233/JND-210784

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

J Neuromuscul Dis. 2022;9(6):713-730. doi: 10.3233/JND-210784.

Authors

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.

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.

MeSH terms

Child
Cohort Studies
Enzyme Replacement Therapy
Glycogen Storage Disease Type II* / drug therapy
Humans
Motor Skills

Associated data

ClinicalTrials.gov/NCT01526785