Viltolarsen Shows Significant Pulmonary Function Gains in Ambulant and Nonambulant DMD


In a recent phase 2 trial analysis of viltolarsen presented at MDA 2024, findings showed improvement in forced vital capacity compared with standard care in patients with Duchenne muscular dystrophy.

Amy D. Harper, MD, professor of neurology of Children’s Hospital of Richmond at Virginia Commonwealth University

Amy D. Harper, MD

Credit: Virginia Commonwealth University

New data from a phase 2 trial (NCT04956289) assessing viltolarsen (Viltepso; NS Pharma), an FDA-approved treatment indicated for Duchenne muscular dystrophy (DMD), showed significant improvement of pulmonary function in patients with dystrophin mutations that are amenable to exon 53 skipping compared with standard of care treatment at 48 weeks. These findings suggest viltolarsen may have beneficial effects and be considered an important part of the treatment strategy for DMD among both ambulant and nonambulant patients.1

In the trial, the mean age of participants treated with viltolarsen was 12.8 years (±5.47; range, 8-26), and 50% of the population was nonambulatory. The mean age of the standard-of-care–treated cohort was 12.7 years(±4.05; range, 8-21), of whom 48% were nonambulatory. Investigators observed a significant improvement of mean change from baseline in percent predicted forced vital capacity (FVC%p) for patients treated with viltolarsen (n = 20; 5.15%; ±2.3) compared with the standard-of-care cohort at week 49 (n = 48; −0.93%; ±1.5; P = .03). Notably, the investigators observed a sustained performance of upper limb 2.0 over the treatment period.

Presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, by lead author Amy D. Harper, MD, professor of neurology of Children’s Hospital of Richmond at Virginia Commonwealth University, the study investigated the safety and motor and pulmonary function in ambulant and nonambulant patients with DMD aged at least 8 years who were treated with viltolarsen 80 mg/kg/week. Investigators compared FVC%p, which accounted for age and height, in participants treated with viltolarsen and standard-of-care–treated participants from the Cooperative International Neuromuscular Research Group–Duchenne Natural History Study Duchenne Natural History Study (CINRG-DNHS),2 which matched for age, ambulatory, pulmonary, and steroid status.

Top Clinical Takeaways

  • Viltolarsen, an FDA-approved treatment for Duchenne muscular dystrophy, exhibited significant improvement in pulmonary function compared with standard care at 48 weeks.
  • The trial indicated a sustained upper limb performance over the treatment period, emphasizing potential broader benefits beyond pulmonary function.
  • Safety findings for viltolarsen were consistent with previous clinical trials, with no serious adverse events reported, suggesting a favorable safety profile for the treatment.

READ MORE: Tadalafil Improves Microvascular Function in Duchenne Leg Muscles, Study Suggests

In the safety population (n = 20), investigators reported 19% of patients treated with viltolarsen had treatment-emergent adverse events (AEs) and noted that 4 of these were related to the study treatment. The authors also noted no reports of serious AEs or deaths, and none of the participants discontinued the study treatment. Overall, the safety findings of the viltolarsen treatment in this analysis were consistent with previous clinical trials.

Published in the Journal of Neuromuscular Diseases, data from the phase 2 long-term extension (LTE) study (NCT03167255) showed viltolarsen stabilized motor function in patients with DMD over the first 2 years and significantly slowed disease progression in the subsequent 2 years.3 In terms of safety, most reported treatment-emergent adverse events were mild or moderate with viltolarsen. These findings suggest viltolarsen may be a effective and safe treatment strategy for patients with DMD amenable to exon 53 skipping over a 4 year period.

This open-label 192-week study assessed the efficacy and safety of viltolarsen in participants aged between 4 year and less than 10 years at baseline with DMD amenable to exon 53 skipping. All participants from the initial 24-week study were enrolled into the LTE (n = 16) and had timed function tests compared with a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study). Invesigators noted that patients included in the study received glucocorticoid treatment. The primary efficacy outcome was time to stand from supine, and secondary efficacy outcomes were additional timed function tests.

“We’ve been pleased by the positive response from the Duchenne community and by pulmonologists who treat Duchenne. There had been limited data regarding older males with respiratory compromise. We are excited to add to the data library," Robert Crozier, PhD, senior director of medical affairs at NS Pharma, told NeurologyLive®.

Click here for more coverage of MDA 2024.

1. Harper AD, Previtera ML, Crozier RA, Magnus L, Clemens P. Pulmonary and motor function in ambulatory and non-ambulatory participants with Duchenne muscular dystrophy treated with viltolarsen. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Poster M148.
2. Spurney C, Shimizu R, Morgenroth LP, et al. Cooperative International Neuromuscular Research Group Duchenne Natural History Study demonstrates insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular dystrophy. Muscle Nerve. 2014;50(2):250-256. doi:10.1002/mus.24163
3. Clemens PR, Rao VK, Connolly AM, et al. Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study. J Neuromuscul Dis. 2023;10(3):439-447. doi:10.3233/JND-221656
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