Article (Scientific journals)
Lessons Learned from Discontinued Clinical Developments in Duchenne Muscular Dystrophy.
Markati, Theodora; De Waele, Liesbeth; Schara-Schmidt, Urlike et al.
2021In Frontiers in Pharmacology, 12, p. 735912
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Keywords :
antisense oligonucleotides; clinical trials; duchenne muscular dystrophy; dystrophin; exon skipping; myostatin inhibition; randomized controlled clinical trials; utrophin upregulation
Abstract :
[en] Duchenne muscular dystrophy (DMD) is an X-linked condition caused by a deficiency of functional dystrophin protein. Patients experience progressive muscle weakness, cardiomyopathy and have a decreased life expectancy. Standards of care, including treatment with steroids, and multidisciplinary approaches have extended the life expectancy and improved the quality of life of patients. In the last 30 years, several compounds have been assessed in preclinical and clinical studies for their ability to restore functional dystrophin levels or to modify pathways involved in DMD pathophysiology. However, there is still an unmet need with regards to a disease-modifying treatment for DMD and the attrition rate between early-phase and late-phase clinical development remains high. Currently, there are 40 compounds in clinical development for DMD, including gene therapy and antisense oligonucleotides for exon skipping. Only five of them have received conditional approval in one jurisdiction subject to further proof of efficacy. In this review, we present data of another 16 compounds that failed to complete clinical development, despite positive results in early phases of development in some cases. We examine the reasons for the high attrition rate and we suggest solutions to avoid similar mistakes in the future.
Disciplines :
Pediatrics
Neurology
Author, co-author :
Markati, Theodora;  University of Oxford, MDUK Oxford Neuromuscular Center > Department of Paediatrics
De Waele, Liesbeth;  KU Leuven > Department of Development and Regeneration & Department of Paediatric Neurology
Schara-Schmidt, Urlike;  University of Duisburg-Essen > 4Department of Pediatric Neurology, Center for Neuromuscular Diseases
Servais, Laurent ;  Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Language :
English
Title :
Lessons Learned from Discontinued Clinical Developments in Duchenne Muscular Dystrophy.
Publication date :
November 2021
Journal title :
Frontiers in Pharmacology
ISSN :
1663-9812
Publisher :
Frontiers, Switzerland
Volume :
12
Pages :
735912
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright © 2021 Markati, De Waele, Schara-Schmidt and Servais. eCollection 2021.
Available on ORBi :
since 18 February 2022

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