In August 2020, the US Food and Drug Administration (FDA) approved a new therapy for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation in the dystrophin gene that is amenable to exon 53 skipping. Viltolarsen, marketed under the brand name Viltepso by NS Pharma, is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass.

Viltolarsen is designed to bind to exon 53 of dystrophin pre-mRNA resulting in exclusion of exon 53 during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. The drug increases dystrophin production in skeletal muscle and was approved through the FDA’s accelerated approval pathway based on this effect observed in clinical trials. While a surrogate end point may predict clinical benefit, continued approval of viltolarsen may be contingent upon verification in a confirmatory trial.

Clinical Trials

Viltepso was evaluated in a 2-period, dose-finding phase 2 trial conducted in North America (n=16) and a phase 1/2 dose-finding study in Japan (n=16).

The phase 2 trial ( Identifier: NCT02740972) formed the basis for approval and included a 4-week double-blind period during which patients were randomly assigned to receive Viltepso or placebo, followed by 20 weeks of open-label treatment. The primary efficacy end point was the change from baseline in dystrophin protein level (measured as percentage of the dystrophin level in healthy individuals [percentage of normal]) at week 25.

Ambulatory male patients ≥4 years and <10 years of age with a confirmed mutation of the DMD gene amenable to exon 53 skipping and on a stable corticosteroid regimen for ≥3 months were included in the study. During the open-label period, patients received 40 mg/kg or 80 mg/kg of Viltepso administered by weekly intravenous infusion. A total of 16 boys underwent randomization, with 8 boys in each cohort; muscle biopsies were performed at baseline and following 24 weeks of treatment.

Results showed all patients had statistically significant increases in dystrophin at week 25. Among patients treated with the 80-mg/kg once-weekly regimen, mean dystrophin levels increased from 0.6% (±0.8) at baseline to 5.9% (±4.5), with a mean change in dystrophin of 5.3% (±4.5) of normal levels (P =.01), as assessed by Western blot normalized to myosin heavy chain (primary end point).

With regard to safety, adverse reaction data were pooled from both clinical trials and showed upper respiratory tract infection (63%), injection site reaction (25%), cough (19%), and pyrexia (19%) to be the most commonly reported side effects in patients treated with the 80-mg/kg once-weekly regimen (n=16). Viltepso was not found to be highly immunogenic based on samples collected from patients in both studies.

Dosage and Administration

Viltepso is supplied as a 250-mg/5-mL preservative-free solution in a single-dose vial. The recommended dosage is 80 mg/kg once weekly administered as an intravenous infusion over 60 minutes. After calculating the total dose based on the patient’s weight, if the volume of Viltepso required is <100 mL, dilution in 0.9% Sodium Chloride Injection, USP is required; if the volume of Viltepso required is ≥100 mL, dilution is not required. 

Prior to initiating treatment, serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured. Additionally, measuring glomerular filtration rate should be considered. While on therapy, all patients should be monitored for kidney toxicity, with close monitoring recommended for those with renal impairment.

Contraindications, Warnings, Precautions, and Adverse Reactions

There are no contraindications to the use of Viltepso.

Though not observed in clinical studies, kidney toxicity was observed in animals that received Viltepso and has been reported with other antisense oligonucleotides. As such, kidney function should be monitored during treatment; however, serum creatinine may not be a reliable measure of kidney function in patients with DMD because of the effect of reduced skeletal muscle mass on creatinine measurements.

Drug Interactions

Viltepso does not inhibit or induce any major enzymes. It is not metabolized by CYP enzymes, nor is it a substrate or inhibitor of major transporters. Viltepso has a low potential for drug-drug interactions with major CYP enzymes and drug transporters.

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Key Takeaways

  • Viltepso was approved based on an increase in dystrophin production in skeletal muscle observed in clinical trials.
  • Monitoring for kidney toxicity is recommended; nephrotoxicity has occurred with drugs similar to Viltepso.
  • Dilution is necessary if the volume of Viltepso required is <100 mL.


1. Viltepso [package insert]. Paramus, NJ: NS Pharma; 2020.

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Neurology Advisor had no role in this content’s preparation.

Reviewed September 2020