FDA Grants Accelerated Approval to Viltepso (viltolarsen) for Duchenne Muscular Dystrophy Patients Amenable to Exon 53 Skipping

Today, the U.S. FDA announced the accelerated approval of Viltepso (viltolarsen), developed by NS Pharma, a subsidiary of Nippon Shinyaku Co., Ltd., for the treatment of specific patients with Duchenne muscular dystrophy (DMD). These patients have confirmed DMD-causing mutations amenable to exon 53 skipping therapy. This marks the second FDA-approved targeted therapy for patients with this specific mutation. Approximately 8% of DMD patients carry mutations that can be treated using the exon 53 skipping strategy.

Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder characterized by progressive muscle degeneration and weakness, and it is the most common form of muscular dystrophy. DMD is caused by mutations in the DMD gene, leading to the absence of dystrophin, a protein that helps maintain the integrity of muscle cells. The initial symptoms typically appear between the ages of 3 and 5 years and worsen over time. Approximately one in every 3,600 male infants worldwide is affected by DMD.

Viltepso is a phosphorodiamidate morpholino oligomer (PMO) drug. It targets the splicing process of dystrophin pre-mRNA, aiming to induce exon 53 skipping to produce a truncated yet functional dystrophin protein. Previously, the FDA granted it Rare Pediatric Disease designation, Orphan Drug designation, Fast Track designation, and Priority Review designation.

▲Mechanism of Action of Viltolarsen (Image source: Nippon Shinyaku official website)

The application for Viltepso is supported by two clinical trials. In one of these trials, which included 16 male patients with Duchenne muscular dystrophy (DMD), eight patients received the recommended dose of Viltepso. Among these eight patients, 100% showed an increase in dystrophin levels following treatment. In 88% (7/8) of the patients, dystrophin levels reached more than 3% of the normal value. After 20–24 weeks of treatment, dystrophin levels increased from 0.6% of the normal baseline value to 5.9% of the normal value at Week 25.

The FDA believes that an increase in dystrophin production may reasonably predict clinical benefit in patients with DMD gene mutations. In making the decision to grant accelerated approval, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available treatments for patients.

As part of the accelerated approval pathway, the FDA is requiring the company to conduct clinical trials to confirm the drug’s clinical benefit. This ongoing study aims to evaluate whether Viltepso improves standing time in patients with Duchenne muscular dystrophy (DMD) who have this confirmed mutation. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.

References:

[1] FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation. Retrieved 2020-08-13, from https://www.prnewswire.com/news-releases/fda-approves-targeted-treatment-for-rare-duchenne-muscular-dystrophy-mutation-301111213.html

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