Viltepso (Viltolarsen) Demonstrates Positive Long-Term Efficacy in DMD and New Drug Application Submitted in China

On July 1, 2021, NS Pharma, a subsidiary of Nippon Shinyaku Co., Ltd., announced that its antisense oligonucleotide therapy, Viltepso (viltolarsen), demonstrated positive long-term efficacy in a Phase 2 clinical trial for patients with Duchenne muscular dystrophy (DMD). Interim trial analysis indicated that, compared with a historical control group, patients treated with Viltepso showed consistent and statistically significant improvements across multiple motor function endpoints at 73 weeks and 109 weeks of treatment. Notably, on June 25, Nippon Shinyaku Co., Ltd. announced that it had submitted a New Drug Application (NDA) for viltolarsen to China's National Medical Products Administration (NMPA).

Viltepso is a phosphorodiamidate morpholino oligomer (PMO) drug. It targets the splicing process of dystrophin pre-mRNA and is designed to induce exon 53 skipping to produce a truncated but functional dystrophin protein. In August 2020, the U.S. FDA granted accelerated approval for Viltepso for the treatment of patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping therapy.

This open-label Phase 2 clinical trial is an extension of a prior 24-week short-term study, with all 16 patients from the short-term trial enrolled in this long-term extension. The results indicated that at Weeks 73 and 109, the mean change from baseline in the time to stand from the supine position in the treatment group increased by 0.21 seconds and 0.43 seconds, respectively, compared to increases of 3.6 seconds and 4.3 seconds in the historical control group (p<0.01). At Weeks 49, 73, and 109, the mean change from baseline in the time to run/walk 10 meters in the treatment group decreased by 0.8, 0.9, and 0.4 seconds, respectively, whereas the historical control group showed increases of 0.5, 1.3, and 1.3 seconds, respectively (p<0.05). At Week 109, in the 6-minute walk test, the mean change from baseline in walking distance for the treatment group was an increase of 0.9 meters, compared to a decrease of 65.6 meters in the historical control group (p<0.05).

Regarding safety, the observed safety profile was consistent with that of prior short-term studies. The most frequently reported adverse events were mild to moderate in severity, including cough, nasopharyngitis, rash, fever, and vomiting. To date, no treatment-related serious adverse events or treatment discontinuations have occurred.

▲Viltepso Mechanism of Action (Image source: company website)

Duchenne muscular dystrophy (DMD) is a rare genetic disorder characterized by progressive muscle degeneration and weakness, and is the most common type of muscular dystrophy. DMD is caused by mutations in the DMD gene, leading to the absence of dystrophin, a protein that helps maintain muscle cell integrity. Initial symptoms typically appear between 3 and 5 years of age and worsen over time. The disease affects approximately 1 in 3,600 male infants worldwide. Approximately 8% of DMD patients carry mutations that are amenable to treatment with an exon 53 skipping strategy.

Note: The original text has been abridged.

References:

[1] VILTEPSO^® (viltolarsen) injection: Long-Term Efficacy and Safety Data Presented at the PPMD 2021 Virtual Annual Conference. Retrieved July 1st, 2021, from https://www.prnewswire.com/news-releases/viltepso-viltolarsen-injection--long-term-efficacy-and-safety-data-presented-at-the-ppmd-2021-virtual-annual-conference-301323668.html

[2] Submission of New Drug Application for NS-065/NCNP-01 (viltolarsen) in China.Retrieved July 1, 2021, from https://www.nippon-shinyaku.co.jp/file/download.php?file_id=3642

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