Viltolarsen

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.

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. 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. In this manner, PMOs are much less susceptible to endo- and exonucleases and exhibit drastically reduced metabolic degradation compared to traditional synthetic oligonucleotides. 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.

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™.