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Viltolarsen Induces De Novo Dystrophin Production in Duchenne Muscular Dystrophy

The Nippon Shinkyaku therapy also showed no treatment-emergent adverse events that required reduction, interruption, or discontinuation of the treatment.

Paula R. Clemens, MD

Results from a phase 2 clinical study (NCT02740972) of viltolarsen (Nippon Shinyaku) demonstrated significant improvements in timed function tests from baseline, as well as induced de novo dystrophin production in patients with Duchenne muscular dystrophy (DMD) that were amenable to exon 53 skipping.1

Research led by Paula R. Clemens, MD, professor of neurology, University of Pittsburgh School of Medicine, and colleagues showed that among the 16 boys, aged 4 to 9 years, included in the study, significant drug-induced dystrophin production was seen in both viltolarsen dose cohorts (40 mg/kg per week: mean, 5.7% [range, 3.2—10.3] of normal; 80 mg/kg per week: mean, 5.9% [range, 1.1–14.4] of normal).

Data from previous studies suggests that dystrophin levels as low as 2% of normal are associated with better functional outcomes. Among the 16 participants, 15 (94%) treated with viltolarsen achieved dystrophin levels greater than 2% of normal, and 14 of 16 (88%) reached levels greater than 3% of normal.

When compared to 65 age-matched and treatment-matched natural history controls, all 16 participants who received viltolarsen showed significant improvements in timed function tests from baseline, including time to stand from supine (viltolarsen: —0.19 s; control: 0.66 s), time to run/walk 10 m (viltolarsen: 0.23 m/s; control: –0.04 m/s), and 6-minute walk test (viltolarsen: 28.9 m; control: –65.3 m) at the Week 25 visit.

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Velocity in the time to stand from supine test and time to climb 4 stairs test, as well as North Star Ambulatory Assessment, similarly displayed improvement or stabilization, but the differences between viltolarsen treatment and controls were not significant.

A significant difference between baseline and posttreatment biopsies was observed in both treatment groups (low-dose viltolarsen cohort: change from baseline normalized to myosin heavy chain, 5.4% [P <&thinsp;.001]; high-dose viltolarsen cohort: change from baseline normalized to myosin heavy chain, 5.3% [P&thinsp;=&thinsp;.01]).

Clemens and the study authors also found that vilatolarsen was well-tolerated and had no treatment-emergent adverse events (TEAEs) that required dose reduction, interruption, or discontinuation of the study drug. Additionally, there were no serious TEAEs or deaths that occurred in the study.

Overall, the phase 2 study included a 4-week randomized clinical trial for safety followed by a 20-week open-label treatment period. The 16 patients were split in half, with 8 participants who received either low dose 40 mg/kg viltolarsen or the high dose 80 mg/kg of viltolarsen, both administered by weekly intravenous infusion.

Safety, tolerability, and de novo dystrophin protein production measured by Western blot in participants’ biceps muscles were the primary outcomes of the study. Individual assessments of dystrophin mRNA and protein production, as well as clinical muscle strength and function were secondary outcomes of the study.

In early February, the FDA accepted the new drug application (NDA) for viltolarsen for the treatment of patients with DMD who are amenable to exon 53 skipping therapy. Results from this study, including additional results from a phase 1 and phase 1/2 study were factored into the regulatory decision as well.2

A month later, Nippon Shinyaku announced that eligible patients with DMD who are amenable to exon 53 may receive viltolarsen through the launch of the viltolarsen Expanded Access Program. The launched program allows eligible patients to received viltolarsen while it remains an investigational drug under FDA review.3


1. Clemens PR, Rao VK, Connolly AM, et al. Safety, tolerability, and efficacy of viltolarsen in boys with Duchenne muscular dystrophy amenable to exon 53 skipping. JAMA Neurol. Published 26, 2020. doi: 10.1001/jamaneurol.2020.1264.

2. NDA accepted for filing by the FDA for antisense oligonucleotide viltolarsen (NS-065/NCNP-01) [news release]. Kyoto, Japan and Paramus, NJ: Nippon Shinyaku. February 7, 2020. Accessed June 4, 2020. nippon-shinyaku.co.jp/file/download.php?file_id=2949.

3. Expanded access program launched for viltolarsen, an investigational exon 53 skipping antisense oligonucleotide [news release] Paramus, NJ: NS Pharma; Published March 9, 2020. Accessed June 4, 2020. nspharma.com/pdf/news_release/press_release_NSP20200309.pdf.