FDA Accepts New Drug Application for Potential DMD Treatment Viltolarsen

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by Forest Ray PhD |

New DMD Mouse Model

The U.S. Food and Drug Administration (FDA) accepted NS Pharma‘s new drug application for viltolarsen, a potential treatment for Duchenne muscular dystrophy (DMD) patients who are amenable to exon 53 skipping, the company and its parent, Nippon Shinyaku, said.

The companies expect a decision on approval between July and September, they said in a press release.

People with DMD lack or have limited amounts of dystrophin, a key protein for muscle function and integrity.

Viltolarsen (NS-065/NCNP-01) is an antisense oligonucleotide that promotes the production of functional dystrophin by masking exon 53 in the dystrophin gene. Exons are the stretches of DNA that code for proteins.

Full-length dystrophin results from stitching all 79 exons of the DMD gene together. When an exon is mutated, the remaining exons may still be stitched together like the pieces of a puzzle to code for a functional protein. However, this only works when the DNA sequences bordering the deleted exon are complementary to each other.

Exon skipping therapies such as viltolarsen work to leave a gap bordered by complementary DNA sequences. This makes the cell machinery skip over the mutated exon 53 to produce a smaller but functional version of dystrophin. Nearly 8% of all DMD patients have mutations in this exon.

The companies filed the NDA late last year, following promising results from a Phase 2 clinical trial (NCT02740972) in North America and from a Phase 1/2 trial in Japan. Both trials measured changes in dystrophin levels and motor function across two doses (40 mg/kg and 80 mg/kg), each given weekly.

Results of the study in the U.S. and Canada showed that viltolarsen, injected directly into the bloodstream, restored dystrophin production in the muscles of boys aged 4-10. Treatment up to 24 weeks was safe and well tolerated.

Nippon Shinyaku and NS Pharma are enrolling up to 74 ambulant boys in Japan and the U.S. for a Phase 3 study (NCT04060199), RACER53, to further assess viltolarsen. Information on contacts and locations, included those yet to open, is here.

The FDA evaluated the application under priority review, an expedited process used for compounds that are expected to produce significant improvements in the treatment of a given disease. The agency had previously granted viltolarsen fast trackorphan drug and rare pediatric disease designations.

In Japan, viltolarsen received SAKIGAKE (intended for early introduction of innovative medicines or medical devices) and orphan drug designations. The Japanese Ministry of Health, Labour and Welfare is reviewing an application requesting the treatment’s approval, filed in Sepetember 2019.

If approved by the FDA, viltolarsen would become the second treatment for patients with DMD amenable for exon 53 skipping, following the recent approval of Sarepta Therapeutics‘  Vyondys 53 (golodirsen) in the U.S.