Viltolarsen Slows DMD Progression in Small Study

A new study has demonstrated the safety and efficacy of once-weekly viltolarsen, a gene therapy for Duchenne muscular dystrophy (DMD), showing that the treatment slows disease progression and helps maintain motor function in boys and young men.¹

The study was published in Brain and Development and compared outcomes in patients receiving viltolarsen with age-matched controls who did not receive the treatment over 3 years.

Viltolarsen is designed to address mutations in the dystrophin gene by skipping exon 53, enabling the production of a functional dystrophin protein. This protein plays a critical role in muscle health, and its absence leads to the severe muscle wasting characteristic of DMD.

3 of the 4 consistently treated patients with DMD maintained motor function | Image credit: Svitlana – stock.adobe.com

The study involved 14 male patients aged 6 to 19 years with DMD, 5 of whom received weekly viltolarsen infusions. Among these patients, 4 adhered to a consistent treatment schedule for the 3-year study period. These patients experienced slower disease progression compared with the 9 control patients who did not receive the therapy. While these 4 patients had treatment rates of at least 99.5%, the fifth patient only completed 71.8% of the treatment schedule, taking frequent breaks due to discomfort related to being on the autism spectrum and having certain intellectual disabilities, according to the authors.

Researchers reported that 3 of the 4 consistently treated patients maintained motor function, while the fourth exhibited only mild declines. In contrast, 8 of the 9 control group patients showed significant motor function deterioration over the same period.

“Currently, reports about intermittent viltolarsen treatment are limited,” the authors noted. “Therefore, further research on the molecular mechanism and the accumulation of similar cases is required to determine the efficacy and safety of intermittent viltolarsen treatment.”

The study also found that patients receiving viltolarsen maintained key physical abilities, such as sitting unassisted and climbing stairs without arm support—abilities that were lost in many untreated patients. Patients treated with viltolarsen also demonstrated lower levels of serum creatine kinase, a marker of muscle damage, as well as larger left ventricular diastolic diameter.

The study reported several treatment-emergent adverse effects (TEAEs) in patients receiving viltolarsen, including proteinuria in all 5 patients, allergic rhinitis in 4, and eczema in 3. Other reported effects included upper respiratory infections, constipation, and headaches, though these were generally mild and resolved with or without treatment. Significant treatment-related adverse effects included localized swelling due to extravasation and lymph node enlargement from frequent infusions, both of which resolved without long-term complications. Despite these TEAEs, no major adverse events led to treatment discontinuation. However, 1 patient receiving intermittent viltolarsen experienced noticeable motor-function decline, underscoring the importance of uninterrupted weekly treatment.

These results add to the growing body of evidence supporting viltolarsen’s role in managing DMD. Earlier studies have demonstrated the therapy’s ability to increase dystrophin production and stabilize motor function over time.

Still, the study had several limitations, including the fact that benefits were only seen in 4 young patients with DMD from a single institution, which restricted the scope of the findings. The limited number of ambulatory patients precluded evaluations using specific motor function tests like the time to stand test and the time to 10 meter run/walk test. Additionally, the study spanned only 3 years and relied on retrospective methods, which limited the evaluation of long-term outcomes and introduced potential biases. Comparisons with other studies, such as the RACER53 trial, highlight the need for further long-term analysis, larger cohorts, and more diverse evaluation methods, including imaging tests, to better characterize the long-term efficacy and safety of viltolarsen.²

“We believe that once-weekly and uninterrupted viltolarsen treatment will yield the expected results,” the authors said.¹ “These findings warrant further investigation in the future using a larger number of cases and a longer follow-up period.”

References

1. Funato M, Iwata R, Ando T, et al. Safety and efficacy of viltolarsen treatment in patients with Duchenne muscular dystrophy: A retrospective study with 3-year follow-up. Brain Dev. Published online November 14, 2024. doi:10.1016/j.braindev.2024.10.005
2. NS Pharma shares preliminary results of viltolarsen (NS-065 / NCNP-01) phase 3 clinical trial (RACER53 Study). News release. NS Pharma. May 27, 2024. Accessed November 22, 2024. https://www.nspharma.com/pdfs/%5BNSP%5D_Press_Release_RACER53_Study_Results.pdf