Viltolarsen Demonstrates Long-Term Benefits in Treating DMD


Efficacy results from a 109-week interim analysis showed improvement for patients treated with viltolarsen when compared to the matched DMD historical control group.

Paula Clemens, MD, University of Pittsburgh Medical Center

Paula Clemens, MD

Results from a phase 2 study of viltolarsen (Viltepso; NS Pharma) injection showed significant benefit for treatment of Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping, specifically showing improvements over multiple time points measuring patients’ time to stand. The findings were presented at the Parent Project Muscular Dystrophy (PPMD) 2021 Virtual Annual Conference.1 

In total, 16 participants, all of whom participated in the previous 24-week trial in North America, opted to enroll in the current long-term trial for a period of 2 years. Results were compared with the DMD historical control group (Cooperative International Neuromuscular Research Group – Duchenne Natural History Study [CINRG-DNHS]). 

“These analyses showed that, after more than 2 years of treatment with Viltepso, patients maintained their motor function based on clinically relevant measurements while the DMD historic controls showed functional decline,” Leslie Magnus, MD, vice president, medical affairs, said in a statement.1

READ MORE: Changing Multidisciplinary Care: Integration of Advanced Practice Clinicians in Neurology 

Participants were evaluated at weeks 37, 49, 73, and 109 and showed improvements in 3 areas. The primary end point of time-to-stand from supine showed change from baseline (in seconds) of 0.21 and 0.43 for those taking viltolarsen, versus the natural history group’s 3.6 and 4.3 (P <.01) at weeks 73 and 109, respectively. A secondary end point of time to run/walk 10 meters showed a mean change in seconds of –0.8, –0.9, and –0.4 compared to the CINRG-DNHS group scores of 0.5, 1.3, 1.3, (P <.05) at weeks 49, 73, and 109, respectively. An additional secondary end point included a 6-minute walk test, which showed a mean change from baseline in meters from baseline of 0.9 for viltolarsen, compared to –65.6 (P <.5) for those in the CINRG-DNHS cohort at week 109. 

No serious adverse events (AEs) were reported by patients in the study, and the AEs that were reported ranged from mild to severe. Cough, nasopharyngitis, rash, pyrexia, and vomiting were the most commonly reported AEs. No patients discontinued treatment over the course of the study, which provides valuable efficacy and safety information for long-term use of viltolarsen in treatment of DMD patients who are amenable to exon 53 skipping. 

“Duchenne is a progressive disease of functional deterioration,” said study investigator Paula Clemens, MD, University of Pittsburgh Medical Center, in a statement.1 “More research is needed, but a disease-modifying therapy that could stabilize and delay the loss of muscle function is needed for families with Duchenne and the healthcare professionals who specialize in its treatment.” 

The latest long-term study from NS Pharma coincides with the confirmatory phase 3 randomized, double-blind, placebo-controlled trial, which was initiated in October 2019 and also aims to evaluable the efficacy and safety of viltolarsen. A phase 2 trial recently compared viltolarsen to golodirsen for treatment of DMD, with results showing that treatment with viltolarsen translated into detectable levels of dystrophin, ranging from 1% to 10%, with a mean level of 6% in patients.2 Watch Eric P. Hoffman, PhD, and Vamshi K. Rao, MD, further discuss the details of the study in the video below. 

Those data was the basis for FDA approval granted to viltolarsen in August 2020 for treatment of patients with DMD, only the second FDA-approved therapy for this specific DMD gene mutation that affect 8% to 11% of patients with DMD. The agent is delivered via weekly intravenous infusion and was originally granted accelerated approval through its rare pediatric disease, orphan drug, and fast track designations. 

The approval was granted based on findings from the phase 2 clinical trial and long-term extension study.2 Among 16 participants age 4 to 9 years, significant drug-induced dystrophin production was observed 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), with 15 (94%) patients achieving dystrophin levels greater than 2% of normal and 14 of 16 (88%) achieving levels greater than 3% of normal. At 25 weeks, compared with natural history controls (n = 65), patients treated in the study demonstrated significant improvements in various timed function testes, 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).

1. Viltepso (viltolarsen) injection: long-term efficacy and safety data presented at the PPMD 2021 Virtual Annual Conference. News release. NS Pharma. July 1, 2021. Accessed July 12, 2021.
2. 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: a phase 2 randomized clinical trial. JAMA Neurol. 2020;77(8):982–991. doi:10.1001/jamaneurol.2020.1264
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