Viltolarsen: First Approval

  title={Viltolarsen: First Approval},
  author={Sohita Dhillon},
Viltolarsen (Viltepso ® in Japan) is a phosphorodiamidate morpholino antisense oligonucleotide being developed by Nippon Shinyaku, in collaboration with the National Center of Neurology and Psychiatry (NCNP), for the treatment of Duchenne muscular dystrophy (DMD). Viltolarsen binds to exon 53 of the dystrophin mRNA precursor and restores the amino acid open-reading frame by skipping exon 53, resulting in the production of a shortened dystrophin protein that contains essential functional… 

Pharmacological Profile of Viltolarsen for the Treatment of Duchenne Muscular Dystrophy: A Japanese Experience

The pharmacological profile of viltolarsen is summarized, focusing on the contribution of Japanese patients and researchers in its development, to produce truncated but partially functional dystrophin in DMD patients and restore muscle function.

CPAA_A_288842 235..242

The pharmacological profile of viltolarsen is summarized, focusing on the contribution of Japanese patients and researchers in its development, to produce truncated but partially functional dystrophin in DMD patients and restore muscle function.

Intramuscular Evaluation of Chimeric Locked Nucleic Acid/2′OMethyl-Modified Antisense Oligonucleotides for Targeted Exon 23 Skipping in Mdx Mice

It is demonstrated that LNA/2′OMe AONs with a 30% LNA composition were significantly more potent in inducing exon skipping and dystrophin restoration in treated mdx muscles, compared to a previously tested 2′O-Methyl- and locked nucleic acid (LNA)-modified nucleotides with lower or higher LNA compositions.

Rise and fall of fomivirsen, the first approved gene silencing medicine : A historical review

Fomivirsen has been a pioneer in this field and has demonstrated the usefulness of the antisense tehcnology for medicinal science, but after three years of use, it has been withdrawn from the market and nowadays, gene silencing drugs with a more advanced chemical structure and more complex mechanism of action are used in medicine.

Lessons Learned from Discontinued Clinical Developments in Duchenne Muscular Dystrophy

There is still an unmet need with regards to a disease-modifying treatment for DMD and the attrition rate between early-phase and late-phase clinical development remains high, and the reasons for the high attrition rate are examined.

Structural Perturbations of Exon Skipping Edits within the Dystrophin D20:24 Region

A systematic and comprehensive panel of possible exon cuts in a region of the dystrophin protein is examined, and for the first time, exon edits that appear to maintain structural stability similar to wildtype protein are identified.

Enhanced exon skipping and prolonged dystrophin restoration achieved by TfR1-targeted delivery of antisense oligonucleotide using FORCE conjugation in mdx mice.

It is demonstrated that a single dose of the mouse-specific FORCE-M23D conjugate enhances muscle delivery of exon skipping PMO (M23d) in mdx mice, achieving dose-dependent and robust exon skipped and durable dystrophin restoration.

Thiomorpholino oligonucleotides as a robust class of next generation platforms for alternate mRNA splicing

The research outlined in this manuscript is highly significant as it demonstrates the impact of “Thiomorpholinos” as a robust and cost-effective splice-switching ASO platform that can be tested for enhanced biological activity and reduced toxicity relative to other chemistries.

Journal Pre-proof Systemic PPMO-mediated dystrophin expression in the Dup2 mouse model of Duchenne muscular dystrophy

It is demonstrated that a peptide-linked phosphorodiamidate morpholino oligomer can induce robust exon skipping and restoration of full-length dystrophin expression following a single intravenous injection in the Dup2 mouse model of DMD.



Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping

Results of this 4-week randomized clinical trial for safety followed by a 20-week open-label treatment period in 16 patients with DMD indicated significant drug-induced dystrophin production in both viltolarsen groups after 20 to 24 weeks of treatment.

Therapeutic developments for Duchenne muscular dystrophy

This Review outlines important developments in these research areas and specifically focuses on new therapies that are in the clinical trial phase or have already been approved for Duchenne muscular dystrophy.

An Overview of Recent Advances and Clinical Applications of Exon Skipping and Splice Modulation for Muscular Dystrophy and Various Genetic Diseases.

This chapter summarizes the development of antisense-mediated exon skipping therapy in diseases such as Usher syndrome, dystrophic epidermolysis bullosa, fibrodysplasia ossificans progressiva (FOP), and allergic diseases.

Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy

A phase 1 clinical trial of NS-065/NCNP-01 showed a favorable safety profile and pharmacokinetics, and the authors demonstrated that it effectively skipped exon 53 in the dystrophin gene, suggesting that a phase 2 trial of the drug is warranted.

Antisense Therapy in Neurology

This paper focuses on the current progress of antisense therapies in neurology and reports on the reported promising targets for antisense therapy.

Duchenne and Becker muscular dystrophy.

Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of

A Japanese phase I/II study of NS-065/NCNP-01, exon 53 skipping drug, in patients with Duchenne muscular dystrophy—a dose-finding study [abstract no. P.129 and poster

  • Neuromuscul Disord. 2018;28(Suppl 2):S68
  • 2018