Last updated Feb. 14, 2022, by Teresa Carvalho, MS
Fact-checked by José Lopes, PhD
Viltepso (viltolarsen) is an approved therapy for Duchenne muscular dystrophy (DMD) patients who carry mutations amenable to exon 53 skipping.
The U.S. Food and Drug Administration gave Viltepso conditional approval on Aug. 12, 2020. This means that NS Pharma, which developed the therapy with its parent company, Nippon Shinyaku, is authorized to sell Viltepso on the basis of less comprehensive data — regarding its safety and efficacy — than normally required for full approval.
In June 2020, the European Commission granted viltolarsen orphan drug designation, given to medicinal products meant to treat life-threatening or chronically debilitating rare conditions. Orphan status provides development and marketing incentives, such as reduced fees and market exclusivity for 10 years upon regulatory approval.
How does Viltepso work?
DMD is caused by mutations in the DMD gene, which provides the instructions necessary to make a structural protein called dystrophin. Dystrophin plays a crucial role in muscle health; without it, each contraction damages muscles.
Most genes are made of so-called exons and introns. Exons are pieces of genetic material that encode for proteins. Introns separate exons and do not encode for proteins. To make a protein, cells make a temporary copy of the gene. This temporary copy is called messenger RNA or mRNA. The mRNA undergoes a process in which cells remove introns and connect the exons together. The resulting mature mRNA molecule is then ready for cells to use as a template to make a protein.
In some Duchenne cases, certain regions of the DMD gene are missing. As a result, the remaining exons do not fit together as they should when the introns are removed. This disrupts the coding sequence of the mRNA, and causes the cell to produce a non-functional dystrophin protein.
Viltepso is a so-called antisense oligonucleotide that masks exon 53, causing cells to “skip” this exon when they are making mature mRNA. This skip helps the remaining exons fit together again, allowing a cell’s protein-making machinery to synthesize a shorter but working dystrophin protein.
Viltepso in clinical trials
A Phase 2 trial (NCT02740972) conducted in the U.S. and Canada assessed the safety and tolerability of once-weekly Viltepso for six months against a placebo in 16 boys (ages 4 to 9) with DMD who were able to walk. All had a confirmed mutation amenable to exon 53 skipping.
Results demonstrated that Viltepso, given at 40 mg/kg (low dose) or 80 mg/kg (high dose), raised dystrophin production in muscles after 20 to 24 weeks of infusion. The treatment was well-tolerated, with the most common side effects being cough and upper respiratory tract infection. None were severe enough to cause participants to leave the study.
A Phase 1/2 clinical trial (Japic CTI-163291) evaluated Viltepso in 16 boys with DMD in Japan. Results showed that treatment led to increases in dystrophin protein in muscle in 14 patients. Researchers also observed a tendency toward greater muscle strength in patients on the treatment’s higher 80 mg/kg dose. No serious treatment-related side effects were reported.
All 16 children who enrolled in the initial Phase 2 trial in the U.S. and Canada continued on to an open-label extension study (NCT03167255). They received Viltepso, once a week by intravenous infusion, for an additional 192 weeks (over three and half years). Early findings showed that long-term treatment with Viltepso safely and effectively prevents decline in motor function.
The conditional approval of Viltepso is pending the results of the ongoing Phase 3 RACER53 trial (NCT04060199). This trial, conducted in the U.S. and other countries, is testing the therapy’s safety and effectiveness in boys ages 4 to 7 with DMD, who are able to walk independently. Researchers will randomly assign patients to either once-weekly infusions of Viltepso at 80 mg/kg or a placebo for up to 48 weeks.
This study’s primary goal is to test changes in muscle strength and function, measured by the time it takes for patients to stand. Secondary outcome measures include time to walk or run a set distance, as well as to climb four steps. Researchers will also take blood samples to determine how the body metabolizes Viltepso. The study is expected to be completed in December 2024.
Viltepso is available in vials containing a single dose of 250 mg/5 mL (50 mg/mL).
The treatment is administered at 80 mg/kg of body weight, once weekly, as an infusion into the bloodstream. Each infusion lasts about 60 minutes.
Viltepso may cause kidney toxicity. For this reason, kidney function should be monitored during treatment. A urine dipstick test — a way to test urinary appearance and content — should be given every month, and blood cystatin C and urine protein-to-creatinine ratio (ways to assess kidney function and protein in urine) should be monitored every three months.
The most commonly reported side effects of using Viltepso are upper respiratory tract infection, injection site reaction, cough, and fever.
Additional information may be found on the therapy’s label.
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