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

doi:10.3233/JND-210784

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	713-730
Number of pages	18
Journal	Journal of neuromuscular diseases
Volume	9
Issue number	6
DOIs	https://doi.org/10.3233/JND-210784
State	Published - 2022

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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10.3233/JND-210784

Cite this

Duong, T., Kishnani, P. S., An Haack, K., Foster, M. C., Gibson, J. B., Wilson, C., Hahn, S. H., Hillman, R., Kronn, D., Leslie, N. D., Peña, L. D. M., Sparks, S. E., Stockton, D. W., Tanpaiboon, P., & Day, J. W. (2022). Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort. Journal of neuromuscular diseases, 9(6), 713-730. https://doi.org/10.3233/JND-210784

@article{21c2b135f5914a559fe6418e6dbaa8ae,

title = "Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort",

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.",

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",

author = "Tina Duong and Kishnani, {Priya S.} and {An Haack}, Kristina and Foster, {Meredith C.} and Gibson, {James B.} and Catherine Wilson and Hahn, {Si Houn} and Richard Hillman and David Kronn and Leslie, {Nancy D.} and Pe{\~n}a, {Loren D.M.} and Sparks, {Susan E.} and Stockton, {David W.} and Pranoot Tanpaiboon and Day, {John W.}",

note = "Funding Information: This study was supported by Sanofi. Medical writing assistance under the sole scientific control of the authors was provided by Kim Coleman Healy, PhD, CMPP and Jane M. Gilbert, BSc (Hons), CMPP, of Elevate Scientific Solutions, contracted by Sanofi for publication support services. Dawn Phillips, MSc, PhD, who consulted for Sanofi when the protocol was developed, designed the Pompe Motor Function Level modifications of GMFCS. Authors employed or contracted by the sponsor (KAH, MCF, SS, and CW) participated in study design, data collection, analysis, and interpretation, intellectually important input into the manuscript, final approval, accountability for accuracy and integrity of the work, and the decision to submit the manuscript. Funding Information: 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{\textquoteright}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{\textquoteright} 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. Publisher Copyright: {\textcopyright} 2022 - The authors. Published by IOS Press.",

year = "2022",

doi = "10.3233/JND-210784",

language = "English",

volume = "9",

pages = "713--730",

journal = "Journal of neuromuscular diseases",

issn = "2214-3599",

number = "6",

}

TY - JOUR

T1 - Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

AU - Duong, Tina

AU - Kishnani, Priya S.

AU - An Haack, Kristina

AU - Foster, Meredith C.

AU - Gibson, James B.

AU - Wilson, Catherine

AU - Hahn, Si Houn

AU - Hillman, Richard

AU - Kronn, David

AU - Leslie, Nancy D.

AU - Peña, Loren D.M.

AU - Sparks, Susan E.

AU - Stockton, David W.

AU - Tanpaiboon, Pranoot

AU - Day, John W.

N1 - Funding Information: This study was supported by Sanofi. Medical writing assistance under the sole scientific control of the authors was provided by Kim Coleman Healy, PhD, CMPP and Jane M. Gilbert, BSc (Hons), CMPP, of Elevate Scientific Solutions, contracted by Sanofi for publication support services. Dawn Phillips, MSc, PhD, who consulted for Sanofi when the protocol was developed, designed the Pompe Motor Function Level modifications of GMFCS. Authors employed or contracted by the sponsor (KAH, MCF, SS, and CW) participated in study design, data collection, analysis, and interpretation, intellectually important input into the manuscript, final approval, accountability for accuracy and integrity of the work, and the decision to submit the manuscript. Funding Information: 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. Publisher Copyright: © 2022 - The authors. Published by IOS Press.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Alglucosidase alfa

KW - Gross Motor Function Classification System

KW - Gross Motor Function Measure-88

KW - Pompe Motor Function History

KW - infantile-onset Pompe disease

KW - late-onset Pompe disease

KW - minimal detectable change

UR - http://www.scopus.com/inward/record.url?scp=85141934315&partnerID=8YFLogxK

U2 - 10.3233/JND-210784

DO - 10.3233/JND-210784

M3 - Article

C2 - 36214004

AN - SCOPUS:85141934315

VL - 9

SP - 713

EP - 730

JO - Journal of neuromuscular diseases

JF - Journal of neuromuscular diseases

SN - 2214-3599

IS - 6

ER -

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

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