Journal article
Clinical Development of Therapies for Charcot–Marie–Tooth Disease: Recommendations for Trial Design, Endpoints, and Regulatory Pathways
Journal of the peripheral nervous system, Vol.31(3), e70146
09/2026
DOI: 10.1111/jns.70146
PMID: 42552689
Abstract
Charcot–Marie–Tooth disease (CMT) encompasses a heterogeneous group of inherited peripheral neuropathies. Despite being the most common genetic neurological condition, individual CMT subtypes are rare, presenting unique challenges for therapeutic development. The Together Patients Industry Clinicians versus CMT (ToPIC: CMT) Advocacy Group was formed with a diverse group of patient advocacy groups, clinician‐scientists who treat patients with CMT, and pharmaceutical industry representatives to develop a common guidance on development of new treatments for CMT with clear expectations for meaningful patient outcomes and objective assessments of improvement. The ToPIC: CMT Group developed recommendations for clinical development of drugs and biological products for treating CMT, addressing trial design considerations for this rare progressive disease. Key challenges in CMT include small patient populations, variable disease progression, and the need for sensitive outcome measures. Recommendations emphasize flexible trial designs including adaptive designs, external controls, and single‐participant designs when scientifically justified. Where possible, broad inclusion criteria based on clinical phenotype rather than genetic subtype alone are recommended. Disease‐specific, validated outcome measures should assess function across ages and disease stages. Biomarkers reflecting peripheral nervous system health may serve as surrogate endpoints to support accelerated approval pathways. Patient and care partner perspectives are essential throughout development, particularly regarding treatment goals, risk tolerance, and meaningful endpoints. Successful therapeutic development for CMT and related neuropathies requires innovative approaches that balance rigorous scientific standards with the realities of rare disease research. Regulatory flexibility, informed by patient input and natural history data, can facilitate efficient development while maintaining assurance of safety and effectiveness.
Details
- Title: Subtitle
- Clinical Development of Therapies for Charcot–Marie–Tooth Disease: Recommendations for Trial Design, Endpoints, and Regulatory Pathways
- Creators
- Charles K. Abrams - University of Illinois ChicagoSue Bruhn - Charcot-Marie-Tooth AssociationJoshua Burns - St. Jude Children's Research HospitalRebekah Fleming - Independent Living ResourcesKatherine Forsey - Charcot-Marie-Tooth AssociationVera Fridman - University of Colorado DenverDavid N. Herrmann - University of Rochester MedicineBrian Lin - Muscular Dystrophy AssociationSusan McCune - University of the PotomacAllison Moore - Hereditary Disease FoundationSusan Ruediger - CMT Research FoundationMichael Shy - University of IowaShannon Strom - Independent Living ResourcesToPIC:CMT Steering Committee
- Resource Type
- Journal article
- Publication Details
- Journal of the peripheral nervous system, Vol.31(3), e70146
- DOI
- 10.1111/jns.70146
- PMID
- 42552689
- ISSN
- 1085-9489
- eISSN
- 1529-8027
- Publisher
- Wiley
- Grant note
- CMT Research Foundation
Open access to this publication is made possible by the CMT Research Foundation.
- Language
- English
- Date published
- 09/2026
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9985217068602771
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