Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study

Journal of Neuromuscular Diseases (2023)

Paula R. Clemens Vamshi K. Rao Anne M. Connolly Amy D. Harper Jean K. Mah Craig M. McDonald Edward C. Smith Craig M. Zaidman Tomoyuki Nakagawa Eric P. Hoffman

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Abstract:

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of > 4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]). Objective: To evaluate the efficacy and safety of viltolarsen for an additional 192 weeks in boys with DMD. Methods: This phase 2, open-label, 192-week long-term extension (LTE) study (NCT03167255) evaluated the efficacy and safety of viltolarsen in participants aged 4 to < 10 years at baseline with DMD amenable to exon 53 skipping. All 16 participants from the initial 24-week study enrolled into this LTE. Timed function tests were compared to the CINRG DNHS group. All participants received glucocorticoid treatment. The primary efficacy outcome was time to stand from supine (TTSTAND). Secondary efficacy outcomes included additional timed function tests. Safety was continuously assessed. Results: For the primary efficacy outcome (TTSTAND), viltolarsen-treated patients showed stabilization of motor function over the first two years and significant slowing of disease progression over the following two years compared with the CINRG DNHS control group which declined. Viltolarsen was well tolerated, with most reported treatment-emergent adverse events being mild or moderate. No participants discontinued drug during the study. Conclusions: Based on the results of this 4-year LTE, viltolarsen can be an important treatment strategy for DMD patients amenable to exon 53 skipping.

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Open label

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Muscle Physiology and Disorders

Exercise and Physiological Responses

Muscle metabolism and nutrition

10.3233/jnd-221656

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Reversal of cardiac and skeletal manifestations of Duchenne muscular dystrophy by cardiosphere-derived cells and their exosomes in mdx dystrophic mice and in human Duchenne cardiomyocytes

bioRxiv (Cold Spring Harbor Laboratory) (2017)

M Aminzadeh Russell G. Rogers Kenneth Gouin Mario Fournier Rachel E. Tobin

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy, affecting the heart as well as skeletal muscle. Here we report that cardiosphere-derived cells (CDCs), which are being tested clinically for the treatment of Duchenne cardiomyopathy, improve cardiac and skeletal myopathy in the mdx mouse model of DMD and in human Duchenne cardiomyocytes. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human Duchenne cardiomyocytes. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.

mdx mouse

10.1101/128900

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PCR65 Assessment of the EQ-5D and DMD-QoL for Duchenne Muscular Dystrophy: A Patient and Caregiver Study

Value in Health (2023)

Graham Morgan SW Brighton A. Samsonroy Jill Carlton G. Baranello

10.1016/j.jval.2023.09.2504

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The organisation and management of agricultural extension and farmer-assistance—A note on developments in Botswana. Part 1: Organisation for extension and some extension problems

Agricultural Administration (1980)

Alan Kingshotte

Agricultural extension

10.1016/0309-586x(80)90014-x

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Physical Activity in Boys With Duchenne Muscular Dystrophy Is Lower and Less Demanding Compared to Healthy Boys

Journal of Child Neurology (2017)

Lotte Heutinck Nadine van Kampen Merel Jansen Imelda J. M. de Groot

This study describes the amount of physical activity and perception of physical activity in boys with Duchenne muscular dystrophy (DMD) compared to healthy boys. A questionnaire described 6 domains of physical activity. Four Duchenne muscular dystrophy subgroups were made: early and late ambulatory, nonambulatory with relative good, or limited arm function. Eighty-four boys with Duchenne muscular dystrophy (15.0 ± 6.4 years) and 198 healthy boys (14.0 ± 4.3 years) participated. Daily activities were more passive for boys with Duchenne muscular dystrophy. Physical activity was less and low demanding compared to healthy boys. It decreased with disease severity ( P < .05), whereas screen time increased ( P < .05). Benefits of physical activity in boys with Duchenne muscular dystrophy were having fun and making friends. Barriers were lack of sport facilities and insufficient health. This study helps to quantify poor engagement in physical activity by boys with Duchenne muscular dystrophy, and demonstrates factors that contribute to it. Suggestions to stimulate physical activity are made.

10.1177/0883073816685506

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P46 ENVOL, a Phase 2, open-label trial evaluating the safety and expression of delandistrogene moxeparvovec in Duchenne muscular dystrophy: study design

Neuromuscular Disorders (2023)

Eugenio Mercuri Isabelle Desguerre Andrea Gangfuß Laurent Servais A. Nascimento

Open label

10.1016/j.nmd.2023.07.027

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PMS84 PSYCHOMETRIC ANALYSIS OF THE PEDIATRIC QUALITY OF LIFE GENERIC CORE SCALE AND NEUROMUSCULAR MODULE IN DUCHENNE MUSCULAR DYSTROPHY: IMPLICATIONS FOR DETERMINING PATIENT-PERCEIVED TREATMENT BENEFIT

Value in Health (2020)