Article Information
Accepted for Publication: November 19, 2021.
Published: January 25, 2022. doi:10.1001/jamanetworkopen.2021.44178
Open Access: This is an open access article distributed under the terms of the
CC-BY-NC-ND License. © 2022 Mah JK et al.
JAMA Network Open.
Corresponding Author: Jean K. Mah, MD, Alberta Children’s Hospital Research Institute, University of Calgary,
28 Oki Dr NW, Calgary, Alberta, Canada T3B 6A8 (
jean.mah@
123456ahs.ca
).
Author Contributions: Dr Dang had full access to all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the data analysis.
Concept and design: Clemens, Guglieri, Finkel, McDonald, Schwartz, Mengle-Gaw, Leinonen, Hoffman, Dang.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Mah, McDonald, Leinonen, Hoffman, Dang.
Critical revision of the manuscript for important intellectual content: Mah, Clemens, Guglieri, Smith, Finkel, Tulinius, Nevo, Ryan, Webster, Castro, Kuntz,
Damsker, Schwartz, Mengle-Gaw, Jackowski, Stimpson, Ridout, Ayyar-Gupta, Baranello,
Manzur, Muntoni, Gordish-Dressman, Leinonen, Ward, Hoffman, Dang.
Statistical analysis: Stimpson, Gordish-Dressman, Leinonen, Hoffman, Dang.
Obtained funding: Clemens, Guglieri, Hoffman.
Administrative, technical, or material support: Mah, Clemens, Finkel, Ryan, McDonald, Damsker, Schwartz, Mengle-Gaw, Jackowski, Ayyar-Gupta,
Manzur, Ward, Hoffman.
Supervision: Mah, Clemens, Tulinius, Ryan, Castro, McDonald, Ridout, Baranello, Hoffman.
Conflict of Interest Disclosures: Dr Mah reported receiving grants from ReveraGen BioPharma during the conduct of the
study; grants from Pfizer, Italfarmaco, Sarepta, Catabasis, Roche, Biogen, Novartis,
NS Pharma, PTC Therapeutics, and Alberta Children's Hospital Foundation; and personal
fees from PTC Therapeutics, Biogen, and Roche outside the submitted work. Dr Clemens
reported serving as a board member for Therapeutic Research in Neuromuscular Disorders
Solutions (TRINDS); receiving grants from the National Institutes of Health (NIH),
NS Pharma, Amicus, Sanofi, Spark, and Muscular Dystrophy Association; receiving research
support through a donation from the Foundation to Eradicate Duchenne to the University
of Pittsburgh; and receiving personal fees from Epirium during the conduct of the
study outside the submitted work. Dr Guglieri reported receiving data management support
from North Star Network during the conduct of the study; grants from the NIH, European
Committee H2020, Duchenne Muscular Dystrophy UK, and Sarepta (funding through Translational
Research in Europe: Assessment and Treatment of Neuromuscular Disorders); personal
fees from Sarepta; and travel fees from Santhera outside the submitted work and serving
as principal or chief investigator or clinical investigator for clinical trials sponsored
by Pfizer, Italfarmaco, Summit, Santhera, Roche, and PTC Therapeutics. Dr Smith reported
receiving grants for partial salary support from Reveragen BioPharma as principal
investigator during the conduct of the study. Dr Finkel reported receiving grants
from ReveraGen BioPharma during the conduct of the study and grants from Catabasis
and Sarepta outside the submitted work. Dr Webster reported receiving research funding
from ReveraGen BioPharma during the conduct of the study. Dr Kuntz reported receiving
grants from Astellas Gene Therapies, Biogen, Genentech, Novartis, and Sarepta; personal
fees from Biogen, Genentech, Novartis, and Sarepta; and data safety monitoring board
services from Sarepta during the conduct of the study. Dr McDonald reported receiving
grants from the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS), US Department of Defense, National Institute on Disability Independent Living
and Rehabilitation Research, and Parent Project Muscular Dystrophy and personal fees
from Astellas, BioMarin, Epirium Bio (formerly Capricor), Catabasis, Entrada Therapeutics,
Avidity Therapeutics, Edgewise Therapeutics, FibroGen, Hoffmann La Roche, Marathon,
Pfizer, Santhera Pharmaceuticals, Saraepta Therapeutics, and PTC Therapeutics outside
the submitted work. Dr Damsker reported being an employee and shareholder of ReveraGen
BioPharma. Dr Schwartz reported receiving personal fees from ReveraGen Biopharma during
the conduct of the study and personal fees from RegenXBio and TRINDS outside the submitted
work. Dr Mengle-Gaw reported receiving personal fees from ReveraGen BioPharma during
the conduct of the study and personal fees from RegenXBio outside the submitted work.
Dr Baranello reported receiving personal fees from Roche, serving as principal investigator
in clinical trials for Pfizer and Reveragen, receiving grants from Sarepta via the
Dubowitz Neuromuscular Centre, and serving as an investigator in a clinical trial
for NS Pharma outside the submitted work. Dr Manzur reported receiving grants from
NorthStar Clinical Network during the conduct of the study and serving as clinical
lead for Northstar Clinical Network UK. Dr Muntoni reported receiving grants from
Muscular Dystrophy UK North Star Consortium during the conduct of the study; grants
from the NIH Research Great Ormond Street Hospital-ICH Biomedical Research Centre,
Genethon, and Sarepta; and personal fees from Dyne Therapeutics, Pfizer, and Sarepta
outside the submitted work. Dr Gordish-Dressman reported receiving personal fees from
TRINDS during the conduct of the study and co-owning TRINDS outside the submitted
work. Dr Ward reported receiving grants from ReveraGen BioPharma via the Children's
Hospital of Eastern Ontario (CHEO) Research Institute during the conduct of the study
and grants from Amgen, Novartis, and PTC Therapeutics via the CHEO Research Institute
outside the submitted work. Dr Hoffman reported receiving salary as chief executive
officer and owning stock from ReveraGen BioPharma, serving as a board member for TRINDS,
receiving grants from the NIH National Institute of Neurological Disorders and Stroke
during the conduct of the study; serving as vice president and owning stock for Agada
BioSciences outside the submitted work; and owning a patent issued to ReveraGen BioPharma.
Dr Dang reported receiving grants from the Foundation to Eradicate Duchenne and personal
fees from ReveraGen BioPharma during the conduct of the study and grants from the
NIH NIAMS outside the submitted work. No other disclosures were reported.
Funding/Support: This work was funded by grants R44NS095423 from the National Institutes of Health
(NIH) National Institute of Neurological Disorders and Stroke to Drs Hoffman and Clemens,
5U54HD090254 from the Eunice Kennedy Shriver National Institute of Child Health and
Human Development to Dr Hoffman, and U34AR068616 from the National Institute of Arthritis
and Musculoskeletal and Skin Diseases to Dr Clemens and grant agreement number 667078
from the European Commission Horizons 2020 to Dr Guglieri. Support for the vamorolone
development program was provided by the Muscular Dystrophy Association, Foundation
to Eradicate Duchenne, Parent Project Muscular Dystrophy, Duchenne UK (formed by Joining
Jack and Duchenne Children’s Trust), Duchenne Research Fund, Save Our Sons, Michael’s
Cause, Pietro’s Fight, Alex’s Wish, Ryan’s Quest, and Cure Duchenne. Vamorolone was
developed through a partnership with the NIH National Center for Advancing Translational
Sciences Therapeutics for Rare and Neglected Diseases program, with support for drug
production, formulation, and toxicology studies. The Cooperative International Neuromuscular
Research Group Duchenne Natural History Study was supported by grants H133B031118
and H133B090001 from the US Department of Education National Institute on Disability
and Rehabilitation Research, W81XWH-12-1-0417 from the US Department of Defense, and
R01AR061875 from the NIH NIAMS and Parent Project Muscular Dystrophy. The UK NorthStar
Clinical Network for Duchenne Muscular Dystrophy is funded by Muscular Dystrophy UK.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript for publication.
Group Information: NorthStar UK Network and CINRG DNHS Investigators are listed in
Supplement 3.
Additional Contributions: We would like to thank all patients with Duchenne muscular dystrophy and their families
for participating in the research studies, as well as the study coordinators, clinical
evaluators, and Therapeutic Research in Neuromuscular Disorders Solutions staff for
the vamorolone long-term extension trial.