Duchenne Muscular Dystrophy (DMD)

Viltepso® (viltolarsen) induces the skipping of exon 53 of dystrophin precursor messenger RNA (pre-mRNA). This exon-skipping therapy has been studied in children as young as 4 years old. It results in the production of shortened dystrophin protein containing essential functional portions. Approximately 10% of patients with Duchenne muscular dystrophy (DMD) are amenable to exon 53 skipping. An innovative triple screening approach designed to identify antisense oligonucleotides led to the discovery of Viltepso. It has the highest possible exon skipping efficiency. Patients with exon 45-52, 47-52, 48-52, 49-52, 50-52, and 52 deletions in the dystrophin gene are eligible for exon 53-skipping therapy.

Viltepso is recommended for patients with confirmed mutations that are amenable to exon 53 skipping. The exon-skipping technique involves skipping over exons next to deleted exons in patients with DMD. In a previous study, Viltepso given for 20 to 24 weeks led to significant improvements in patients with DMD. The mean increase in dystrophin expression was evaluated in ambulant males aged 4 to 9 years. The dystrophin expression was 6% of normal with Viltepso therapy of 80 mg/kg/week; it was only 0.6% at the start of the study. The results were statistically significant at week 25. This phase 2 study was a randomized placebo-controlled study with an initial safety period of 4 weeks, followed by 20 weeks of open-label Viltepso treatment with 2 dose cohorts of patients with DMD who were amenable to exon 53 skipping.1

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Food and Drug Administration-Approved Targeted Treatment for DMD

Viltepso demonstrated an increase in dystrophin production, which showed clinical benefits for DMD patients with confirmed mutations in the dystrophin gene amenable to exon 53 skipping. The clinical benefit of the drug was not yet established during the time of the US Food and Drug Administration (FDA) approval. The FDA took note of the potential risks associated with this treatment during the Viltepso approval process. It also acknowledged the lack of available therapies for DMD and the debilitating and life-threatening nature of the disease. A clinical trial is required to confirm the clinical benefit of the drug as part of the accelerated approval process of the FDA. The study aims to assess whether Viltepso improves the condition of DMD patients with the confirmed mutation. If the clinical trial fails to verify the clinical benefits of Viltepso, the FDA can withdraw the approval of the drug. The FDA granted the application based on priority review designation to NS Pharma, Inc.2

Clinical Pharmacology

Viltepso can lead to the exclusion of exon 53 during mRNA processing, as it is designed to bind to exon 53 of dystrophin pre-mRNA. It is effective in DMD patients with genetic mutations that are amenable to exon 53 skipping. Internally truncated dystrophin protein is produced in patients with genetic mutations due to the skipping of exon 53. Patients with DMD are treated with Viltepso (80 mg/kg) once a week. According to a study conducted in patients with DMD, most patients were found to produce mRNA for a truncated dystrophin protein as measured by reverse transcription-polymerase chain reaction (RT-PCR). According to DNA sequence analysis, they demonstrated exon 53 skippings. All patients received a weekly dosage of Viltepso (80 mg/kg) for 20 to 24 weeks. As quantified by a validated western blot method, an increase in dystrophin protein expression from baseline was observed, with a mean of 5.4%, median of 3.8%, P value of 0.01, and range of 0.7% to 13.9% when normalized to myosin heavy chain. The western blot data was supported by immunofluorescence staining, mass spectrometry, and RT-PCR results.3

Side Effects

Viltepso has side effects involving reaction of the injection site with bruising, redness, and/or swelling. Patients may suffer from upper respiratory tract infection as well, with fever, cough, joint pain, diarrhea, bruising, vomiting, and abdominal pain. They may also experience urticaria due to the dosage and decreased ejection fraction. Viltepso may also interact with other medications; patients should disclose all medications and supplements they use to their physician. Viltepso’s effects on the fetus and breastmilk are unknown.4 

Efficacy, Tolerability, and Safety

Viltepso induces significant de novo dystrophin production in patients with DMD amenable to exon 53 skipping. It has demonstrated clinical improvements in timed function tests with matched historical controls. The FDA accepted de novo dystrophin production as a surrogate outcome for Viltepso drug approval. As measured by western blot, the study exhibited a significant increase in dystrophin expression at week 25 with mean (standard deviation) increases of 5.9% (4.5%) in the high dose group and 5.7% (2.4%) in the low dose group. Increased dystrophin production by Viltepso is the highest reported in clinical trials of exon skipping therapies to date. As measured by mass spectrometry quantification and localization techniques, the results show a substantial increase in Viltepso-induced dystrophin levels. Clinical studies show that dystrophin levels partially correlate with clinical severity in patients with DMD. Muscle biopsies from DMD patients show modestly increased higher dystrophin levels from 2% to 7% of normal. Increased dystrophin levels are associated with a better functional outcome in older patients with DMD suffering from loss of ambulation.5 

Motor Function Evaluations With Vitepso Therapy

Various exercise function evaluation procedures were conducted in patients with DMD in a standardized manner by trained clinical evaluators during the pre-treatment period. Some of these procedures are the timed up-and-go test (TUG), 6-minute walk test (6MWT), time-to-run/walk test (TTRW), and time-to-stand test (TTSTAND). These tests were evaluated at week 12 and week 24 after Viltepso administration and at discontinuation of treatment. Authorized physical therapists or doctors trained by a master physical therapist assessed these tests. MicroFET, a handheld dynamometer, was used to conduct quantitative muscle strength testing and measure extension/flexion of the hip, ankle, and knee joint at each time point. Serum creatinine kinase was measured during the preobservation period at weeks 1, 5, 9, 13, 17, and 21 and during the postobservation period at week 25 after discontinuation of Viltepso treatment in patients with DMD.6


  1. Viltepso: healthcare professionals. NS Pharma. Accessed August 18, 2021.
  2. FDA approves targeted treatment for rare Duchenne muscular dystrophy mutation. News release. FDA; August 12, 2020.
  3. Viltepso (viltolarsen). NS Pharma, Inc.; 2020. Accessed August 18, 2021.
  4. Viltepso: side effects. RxList. Updated March 22, 2021. Accessed August 18, 2021.
  5. Clemens PR, Rao VK, Connolly AM, et al.; CINRG DNHS Investigators. 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
  6. Komaki H, Takeshima Y, Matsumura T, et al. Viltolarsen in Japanese Duchenne muscular dystrophy patients: a phase 1/2 study. Ann Clin Transl Neurol. 2020;7(12):2393-2408. doi:10.1002/acn3.51235

Reviewed by Harshi Dhingra, MD, on 8/23/2021.