Viltolarsen is an antisense phosphorodiamidate morpholino oligonucleotide specific for exon 53 of the human DMD gene that is capable of inducing exon 53 skipping to produce a functional truncated dystrophin protein in Duchenne muscular dystrophy patients with specific underlying mutations.

Brand Names
Generic Name
DrugBank Accession Number

Duchenne muscular dystrophy (DMD) is an X-linked recessive allelic disorder characterized by a lack of functional dystrophin protein, which leads to progressive ambulatory, pulmonary, and cardiac function and is invariably fatal. A related, albeit a less severe, form of muscular dystrophy known as Becker muscular dystrophy (BMD) is characterized by the production of shortened and partially functional dystrophin protein. Although corticosteroids are effective in slowing disease progression in both DMD and BMD patients, they do not address the underlying molecular pathogenesis.3,4,7

The application of antisense oligonucleotides in DMD patients with specific mutations allows for exon skipping, which retains a productive reading frame and results in the production of truncated BMD-like dystrophin proteins.1,2,3,4,5,7,8 These shortened forms of dystrophin can restore partial muscle function and slow the progression of DMD. Viltolarsen is a phosphorodiamidate morpholino oligonucleotide (PMO); PMOs are oligonucleotides in which the five-membered ribofuranosyl ring is replaced with a six-membered morpholino ring, and the phosphodiester links between nucleotides are replaced with a phosphorodiamidate linkage.6,8 In this manner, PMOs are much less susceptible to endo- and exonucleases and exhibit drastically reduced metabolic degradation compared to traditional synthetic oligonucleotides.6 Hence, viltolarsen is similar to another PMO, eteplirsen, which gained FDA approval on September 19, 2016; however, eteplirsen is specific for exon 51 skipping while viltolarsen is specific for exon 53 skipping.4

Viltolarsen was granted accelerated FDA approval on August 12, 2020, based on data showing an increase in dystrophin levels in skeletal muscle of patients treated with viltolarsen; this approval is contingent on further verification in confirmatory trials. Viltolarsen was developed by Nippon Shinyaku Co LTD and is being marketed under the name VILTEPSO™.8

Approved, Investigational
Biologic Classification
Gene Therapies
Antisense oligonucleotides
  • Exon 53 specific antisense morpholino oligonucleotide
  • Viltolarsen
External IDs
  • NCNP-01
  • NS-065
  • NS-065/NCNP-01
  • WHO 10771
  • WHO-10771



Viltolarsen is indicated for the treatment of Duchenne muscular dystrophy in patients confirmed to have a DMD gene mutation amenable to exon 53 skipping. This indication represents an accelerated approval based on observed efficacy; continued approval for this indication may be contingent on the verification of safety and efficacy in a confirmatory trial.8

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Viltolarsen is an antisense phosphorodiamidate morpholino oligonucleotide designed to bind to and disrupt splicing of exon 53 in the human DMD gene, which results in the expression of a partially functional dystrophin protein in patients who otherwise would not produce dystrophin.1,2,8 Despite a relatively short half-life, the physiological effect of producing relatively stable dystrophin protein allows for effective therapeutic benefit with weekly dosing.8 Viltolarsen may cause renal toxicity, and so kidney function should be monitored in patients. However, due to the alteration of serum creatinine in Duchenne muscular dystrophy patients,3 creatinine should not be used as a marker of renal function.8

Mechanism of action

Duchenne muscular dystrophy (DMD) is an X-linked recessive allelic disorder that results in the absence of functional dystrophin, a large protein comprising an N-terminal actin-binding domain, C-terminal β-dystroglycan-binding domain, and 24 internal spectrin-like repeats.3,4 Dystrophin is vital for normal muscle function; the absence of dystrophin leads to muscle membrane damage, extracellular leakage of creatinine kinase, calcium influx, and gradual replacement of normal muscle tissue with fibrous and adipose tissue over time. The disease progresses from loss of ambulatory function to ventilatory insufficiency and cardiomyopathy, with death typically occurring in the second or third decade of life.3,4,5

The human DMD gene contains 79 exons spread over approximately 2.4 million nucleotides on the X chromosome.3 DMD is associated with a variety of underlying mutations, including exon duplications or deletions, as well as point mutations leading to nonsense translation through direct production of an in-frame stop codon, frameshift production of an in-frame stop codon, or aberrant inclusion of an intronic pseudo-exon with the concomitant production of an in-frame stop codon.3,4 In all cases, no functional dystrophin protein is produced. Becker muscular dystrophy (BMD) is a related condition with in-frame mutations that result in the production of a truncated but partially functional dystrophin protein. BMD patients, therefore, have milder symptoms, delayed disease progression, and longer life expectancy compared to DMD patients.1,3,4,5

Viltolarsen is an antisense phosphorodiamidate morpholino oligonucleotide designed to bind to a specific region in exon 53 of the DMD pre-mRNA and prevent its inclusion within the mature mRNA before translation. In patients with specific mutations, including those with deletions of exons 45-52, 47-52, 48-52, 49-52, 50-52, or solely of exon 52, this results in restoration of the expected reading frame and the production of a BMD-like dystrophin protein.1,5,6,7,8 Although fibrotic or fatty muscle tissue developed previously cannot be improved, this therapy aims to slow further disease progression through the production of partially functional dystrophin and alleviation of the pathogenic mechanism of muscle tissue necrosis.3,4

ADMD gene (exon 53 viltolarsen target site)

Viltolarsen is administered by intravenous infusion and is assumed to have a bioavailability of 100%.8 In a phase 1 dose-escalation trial of 10 patients given either 1.25, 5, or 20 mg/kg weekly for 12 weeks, the mean Cmax was 6040 ± 300 ng/mL in the low dose group and 70,200 ± 44,900 ng/mL in the high dose group on initial dose, with the corresponding final dose values of 5640 ± 2440 and 72,800 ± 26,400 ng/mL, respectively. Similarly, the AUC0-t for the initial/final dose was 8410 ± 1310/8410 ± 3520 ng*hr/mL for the low dose and 98,900 ± 54,100/115,000 ± 56,000 ng*hr/mL for the high dose.2 The Tmax varied between 0.667 ± 0.289 and 1.00 ± 0.00 hours,2 and viltolarsen has a documented median Tmax of approximately one hour.8

Volume of distribution

Viltolarsen has a steady-state volume of distribution of 300 mL/kg (14% CV) when given at 80 mg/kg.8 In patients given either 1.25, 5, or 20 mg/kg viltolarsen weekly for 12 weeks the volume of distribution was between 183 ± 14 and 264 ± 68 mL/kg.2

Protein binding

Viltolarsen in vitro plasma protein binding is between 39 and 40% and is not concentration-dependent.7,8


Viltolarsen metabolism was not detected in serum or liver-derived microsomes, and it appears not to be metabolized by either DNase I or phosphodiesterase type 1 in vitro.7 This lack of metabolism is consistent with what is known regarding the stability of phosphorodiamidate morpholino oligonucleotides to enzymatic cleavage.6

Route of elimination

Viltolarsen is mainly excreted in the urine unchanged;8 in a phase 1/2 study of 16 Japanese DMD patients, 92.0-93.1% of a single 80 mg/kg dose of viltolarsen was recovered unchanged in the patient urine within 24 hours of administration.7


Viltolarsen has a reported elimination half-life of 2.5 hours (8% CV).8 When administered at either 40 or 80 mg/kg for 24 weeks, viltolarsen elimination half-life was 2.38 and 2.82 hours, respectively.7


Viltolarsen has a reported plasma clearance of 217 mL/hr/kg (22% CV).8 Patients taking 1.25, 5, or 20 mg/kg viltolarsen weekly for 12 weeks had a total clearance of between 149 ± 21 and 239 ± 97 ml/hr/kg.2

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Viltolarsen administered by subcutaneous injection in juvenile male mice resulted in deaths due to renal toxicity at high doses; in animals administered either 240 or 1200 mg/kg viltolarsen, dose-dependent increases in the incidence and severity of renal tubular effects were observed. Although renal toxicity in humans has not been observed, it is recommended to measure urine dipstick every month and serum cystatin C and urine protein-to-creatinine ratio every three months to detect renal toxicity.8

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.


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International/Other Brands
Viltepso (NS Pharma, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ViltepsoInjection, solution250 mg/1IntravenousNs Pharma, Inc.2020-08-13Not applicableUS flag


ATC Codes
M09AX12 — Viltolarsen
Drug Categories
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

CAS number


Synthesis Reference

Watanabe N, Nagata T, Satou Y, Masuda S, Saito T, Kitagawa H, Komaki H, Takagaki K, Takeda S: NS-065/NCNP-01: An Antisense Oligonucleotide for Potential Treatment of Exon 53 Skipping in Duchenne Muscular Dystrophy. Mol Ther Nucleic Acids. 2018 Dec 7;13:442-449. doi: 10.1016/j.omtn.2018.09.017.

General References
  1. Watanabe N, Nagata T, Satou Y, Masuda S, Saito T, Kitagawa H, Komaki H, Takagaki K, Takeda S: NS-065/NCNP-01: An Antisense Oligonucleotide for Potential Treatment of Exon 53 Skipping in Duchenne Muscular Dystrophy. Mol Ther Nucleic Acids. 2018 Dec 7;13:442-449. doi: 10.1016/j.omtn.2018.09.017. Epub 2018 Sep 27. [Article]
  2. Komaki H, Nagata T, Saito T, Masuda S, Takeshita E, Sasaki M, Tachimori H, Nakamura H, Aoki Y, Takeda S: Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci Transl Med. 2018 Apr 18;10(437). pii: 10/437/eaan0713. doi: 10.1126/scitranslmed.aan0713. [Article]
  3. Wein N, Alfano L, Flanigan KM: Genetics and emerging treatments for Duchenne and Becker muscular dystrophy. Pediatr Clin North Am. 2015 Jun;62(3):723-42. doi: 10.1016/j.pcl.2015.03.008. Epub 2015 Apr 20. [Article]
  4. Verhaart IEC, Aartsma-Rus A: Therapeutic developments for Duchenne muscular dystrophy. Nat Rev Neurol. 2019 Jul;15(7):373-386. doi: 10.1038/s41582-019-0203-3. [Article]
  5. Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, Smith EC, McDonald CM, Zaidman CM, Morgenroth LP, Osaki H, Satou Y, Yamashita T, Hoffman EP: 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 May 26. pii: 2766519. doi: 10.1001/jamaneurol.2020.1264. [Article]
  6. Smith CIE, Zain R: Therapeutic Oligonucleotides: State of the Art. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:605-630. doi: 10.1146/annurev-pharmtox-010818-021050. Epub 2018 Oct 9. [Article]
  7. Dhillon S: Viltolarsen: First Approval. Drugs. 2020 Jul;80(10):1027-1031. doi: 10.1007/s40265-020-01339-3. [Article]
  8. FDA Approved Drug Products: Viltepso (vitolarsen) injection [Link]

Clinical Trials

Clinical Trials
4Active Not RecruitingTreatmentDuchenne Muscular Dystrophy (DMD)1
3CompletedTreatmentDuchenne Muscular Dystrophy (DMD)1
3Enrolling by InvitationTreatmentDuchenne Muscular Dystrophy (DMD)1
2CompletedTreatmentDuchenne Muscular Dystrophy (DMD)3
1CompletedTreatmentDuchenne Muscular Dystrophy (DMD)1
Not AvailableApproved for MarketingNot AvailableDuchenne Muscular Dystrophy (DMD)1


Not Available
Not Available
Dosage Forms
Injection, solutionIntravenous250 mg/1
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9079934No2015-07-142031-08-31US flag
US10870676No2020-12-222031-08-31US flag


Experimental Properties
Not Available


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Pharmacological action
Curator comments
Viltolarsen binds to exon 53 of the dystrophin pre-mRNA and induces skipping of this exon to produce a functional truncated protein.
The sequence of the region on the human DMD gene targeted by the antisense oligonucleotide viltolarsen.
  1. Watanabe N, Nagata T, Satou Y, Masuda S, Saito T, Kitagawa H, Komaki H, Takagaki K, Takeda S: NS-065/NCNP-01: An Antisense Oligonucleotide for Potential Treatment of Exon 53 Skipping in Duchenne Muscular Dystrophy. Mol Ther Nucleic Acids. 2018 Dec 7;13:442-449. doi: 10.1016/j.omtn.2018.09.017. Epub 2018 Sep 27. [Article]
  2. FDA Approved Drug Products: Viltepso (vitolarsen) injection [Link]

Drug created at May 20, 2019 14:41 / Updated at June 05, 2023 15:26