AVXS-101 (Onasemnogene Abeparvovec) for SMA1: Comparative Study with a Prospective Natural History Cohort.

Female Genetic Therapy Humans Infant Kaplan-Meier Estimate Male Prospective Studies Spinal Muscular Atrophies of Childhood / genetics Treatment Outcome
Gene therapy natural history neuromuscular diseases spinal muscular atrophy

Journal

Journal of neuromuscular diseases
ISSN: 2214-3602
Titre abrégé: J Neuromuscul Dis
Pays: Netherlands
ID NLM: 101649948

Informations de publication

Date de publication:
2019
Historique:
pubmed: 6 8 2019
medline: 18 2 2020
entrez: 6 8 2019
Statut: ppublish

Résumé

Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma®) gene replacement therapy, are emerging. This study evaluated the effectiveness of AVXS-101 in infants with spinal muscular atrophy type 1 (SMA1) compared with a prospective natural history cohort and a cohort of healthy infants. Twelve SMA1 infants received the proposed therapeutic dose of AVXS-101 (NCT02122952). Where possible, the following outcomes were compared with a natural history cohort of SMA1 infants (n = 16) and healthy infants (n = 27) enrolled in the NeuroNEXT (NN101) study (NCT01736553): event-free survival, CHOP-INTEND scores, motor milestone achievements, compound muscle action potential (CMAP), and adverse events. Baseline characteristics of SMA1 infants in the AVXS-101 and NN101 studies were similar in age and genetic profile. The proportion of AVXS-101-treated infants who survived by 24 months of follow-up was higher compared with the NN101 study (100% vs 38%, respectively). The average baseline CHOP-INTEND score for NN101 SMA1 infants was 20.3, worsening to 5.3 by age 24 months; the average baseline score in AVXS-101-treated infants was 28.2, improving to 56.5 by age 24 months. Infants receiving AVXS-101 achieved motor milestones, such as sitting unassisted and walking. Improvements in CMAP peak area were observed in AVXS-101-treated infants at 6 and 24 months (means of 1.1 and 3.2 mV/s, respectively). In this study, AVXS-101 increased the probability of survival, rapidly improved motor function, and enabled motor milestone achievement in SMA1 infants.

Sections du résumé

BACKGROUND BACKGROUND
Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma®) gene replacement therapy, are emerging.
OBJECTIVE OBJECTIVE
This study evaluated the effectiveness of AVXS-101 in infants with spinal muscular atrophy type 1 (SMA1) compared with a prospective natural history cohort and a cohort of healthy infants.
METHODS METHODS
Twelve SMA1 infants received the proposed therapeutic dose of AVXS-101 (NCT02122952). Where possible, the following outcomes were compared with a natural history cohort of SMA1 infants (n = 16) and healthy infants (n = 27) enrolled in the NeuroNEXT (NN101) study (NCT01736553): event-free survival, CHOP-INTEND scores, motor milestone achievements, compound muscle action potential (CMAP), and adverse events.
RESULTS RESULTS
Baseline characteristics of SMA1 infants in the AVXS-101 and NN101 studies were similar in age and genetic profile. The proportion of AVXS-101-treated infants who survived by 24 months of follow-up was higher compared with the NN101 study (100% vs 38%, respectively). The average baseline CHOP-INTEND score for NN101 SMA1 infants was 20.3, worsening to 5.3 by age 24 months; the average baseline score in AVXS-101-treated infants was 28.2, improving to 56.5 by age 24 months. Infants receiving AVXS-101 achieved motor milestones, such as sitting unassisted and walking. Improvements in CMAP peak area were observed in AVXS-101-treated infants at 6 and 24 months (means of 1.1 and 3.2 mV/s, respectively).
CONCLUSIONS CONCLUSIONS
In this study, AVXS-101 increased the probability of survival, rapidly improved motor function, and enabled motor milestone achievement in SMA1 infants.

Identifiants

DOI: 10.3233/JND-190403 PMID: 31381526
pubmed: 31381526
pii: JND190403
doi: 10.3233/JND-190403
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

307-317

Commentaires et corrections

Type : CommentIn

Auteurs

Samiah A Al-Zaidy (SA)

Center for Gene Therapy Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Stephen J Kolb (SJ)

Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Department of Biological Chemistry and Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Linda Lowes (L)

Center for Gene Therapy Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Lindsay N Alfano (LN)

Center for Gene Therapy Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Richard Shell (R)

Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Kathleen R Church (KR)

Center for Gene Therapy Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.

Sukumar Nagendran (S)

AveXis, Inc., Bannockburn, IL, USA.

Douglas M Sproule (DM)

AveXis, Inc., Bannockburn, IL, USA.

Douglas E Feltner (DE)

AveXis, Inc., Bannockburn, IL, USA.

Courtney Wells (C)

AveXis, Inc., Bannockburn, IL, USA.

Francis Ogrinc (F)

AveXis, Inc., Bannockburn, IL, USA.

Melissa Menier (M)

AveXis, Inc., Bannockburn, IL, USA.

James L'Italien (J)

AveXis, Inc., Bannockburn, IL, USA.

W David Arnold (WD)

Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

John T Kissel (JT)

Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Brian K Kaspar (BK)

AveXis, Inc., Bannockburn, IL, USA.

Jerry R Mendell (JR)

Center for Gene Therapy Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Thérapie génétique › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Estimation de Kaplan-Meier › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies neurodégénératives héréditaires › Amyotrophies spinales infantiles › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › AVXS-101 (Onasemnogene Abeparvovec) for SMA1:...