269th ENMC international workshop: 10 years of clinical trials in Duchenne muscular dystrophy - What have we learned? 9-11 December 2022, Hoofddorp, The Netherlands

Karin J Naarding; Georgia Stimpson; Susan J Ward; Nathalie Goemans; Craig McDonald; Eugenio Mercuri; Francesco Muntoni; 269th ENMC workshop participants

doi:10.1016/j.nmd.2023.10.003

269th ENMC international workshop: 10 years of clinical trials in Duchenne muscular dystrophy - What have we learned? 9-11 December 2022, Hoofddorp, The Netherlands

Neuromuscul Disord. 2023 Nov;33(11):897-910. doi: 10.1016/j.nmd.2023.10.003. Epub 2023 Oct 11.

Authors

Karin J Naarding¹, Georgia Stimpson², Susan J Ward³, Nathalie Goemans⁴, Craig McDonald⁵, Eugenio Mercuri⁶, Francesco Muntoni⁷; 269th ENMC workshop participants

Collaborators

269th ENMC workshop participants:
Nathalie Goemans⁸, Craig McDonald⁹, Eugenio Mercuri¹⁰, Francesco Muntoni¹¹, Susan J Ward¹², Paolo Bettica¹³, Michael Binks¹⁴, Tina Duong¹⁵, Ana Ferreiro¹⁶, Patricia Furlong¹⁷, Michela Guglieri¹⁸, Suzanne Hendrix¹⁹, Erik Henricson²⁰, Jean-Yves Hogrel²¹, Matthew Klein²², Mindy Leffler²³, Terina Martinez²⁴, Karin J Naarding²⁵, Erik Niks²⁵, Laurent Servais²⁶, James Signorovitch²⁷, Georgia Stimpson²⁸, Frank Van Ieperen²⁹, Elizabeth Vroom³⁰

Affiliations

¹ Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Duchenne Center Netherlands, the Netherlands.
² UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Centre, London, UK.
³ Collaborative Trajectory Analysis Project (cTAP), United States.
⁴ University Hospitals Leuven, Dept of Child Neurology, Leuven, Belgium.
⁵ Department of Physical Medicine and Rehabilitation in Sacramento, University of California, Davis, CA, United States.
⁶ Pediatric Neurology Unit, Catholic University, Rome, Italy; Centro Clinico Nemo, U.O.C. Neuropsichiatria Infantile Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁷ UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Centre, London, UK; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK. Electronic address: [email protected].
⁸ University Hospitals Leuven, Leuven, Belgium.
⁹ University of California, Davis -Sacramento, USA, via web-link.
¹⁰ Catholic University, and U.O.C. Neuropsichiatria Infantile Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
¹¹ UCL London, UK.
¹² Collaborative Trajectory Analysis Project (cTAP), Cambridge, USA.
¹³ Italfarmaco, Milan, Italy.
¹⁴ Pfizer- Cambridge, Massachusetts, USA.
¹⁵ Stanford University- Palo Alto, USA.
¹⁶ Université Paris Cité, and Pitié-Salpêtrière University Hospital, Paris, France.
¹⁷ Parent Project Muscular Dystrophy, Middletown, USA.
¹⁸ Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
¹⁹ Pentara Corporation, Salt Lake City, USA.
²⁰ UC Davis Children's Hospital, Sacramento, USA.
²¹ Pitié-Salpêtrière University Hospital, Paris, France.
²² PTC Therapeutics, New York, USA, via web-link.
²³ Casimir, Bellevue, USA.
²⁴ Critical Path Institute, Tuscon, USA.
²⁵ Leiden University Medical centre, and Duchenne centre Netherlands, Leiden, The Netherlands.
²⁶ MD UK Oxford Neuromuscular centre, Oxford, UK.
²⁷ Collaborative Trajectory Analysis Project (cTAP), Boston, USA.
²⁸ UCL, London, UK.
²⁹ Patient, The Netherlands.
³⁰ Patient Representative, The Netherlands.

PMID: 37926638
DOI: 10.1016/j.nmd.2023.10.003

Abstract

There are multiple avenues for therapeutic development in Duchenne muscular dystrophy (DMD), which are highlighted in the first section of this report for the "10 years of Clinical trials in DMD - What have we learned?" workshop. This report then provides an overview of the presentations made at the workshop grouped into the following core themes: trial outcomes, disease heterogeneity, meaningfulness of outcomes and the utility of real-world data in trials. Finally, we present the consensus that was achieved at the workshop on the learning points from 10 years of clinical trials in DMD, and possible action points from these. This includes further work in expanding the scope and range of trial outcomes and assessing the efficacy of new trial structures for DMD. We also highlight several points which should be addressed during future interactions with regulators, such as clinical meaningfulness and the use of real-world data.

Keywords: Clinical trial; Duchenne muscular dystrophy; Meaningfulness; Outcome measure; Real world data.

MeSH terms

Humans
Muscular Dystrophy, Duchenne* / drug therapy
Netherlands