Viltolarsen: a treatment option for Duchenne muscular dystrophy patients who are amenable to exon 53 skipping therapy

ABSTRACT

Introduction

Duchenne muscular dystrophy (DMD) is a progressive genetic disease leading to muscular weakness. DMD is caused by mutations of the dystrophin gene on the X chromosome that is responsible for production of dystrophin protein. Dystrophin contributes to structural support in muscle cells and mutations result in dystrophin protein deficiency which causes muscle damage and the associated clinical presentation. Exon skipping medications, including the exon 53 targeting viltolarsen, are the first agents with the ability to partially restore dystrophin protein.

Areas covered

Herein, the authors profile viltolarsen for the DMD patients who are amenable to exon 53 skipping therapy and provide their expert perspectives on this subject.

Expert opinion

Current findings suggest that viltolarsen could play a role in the current and possible future treatment of DMD. Viltolarsen seems to be safe and restores dystrophin protein to around 6% of the normal level. Due to orphan drug status, after the completion of the phase 2 clinical trial, viltolarsen was granted accelerated approval in Japan and in the US. A phase 3 trial is currently in progress and needs to earn full approval. Although a multidisciplinary approach continues to be critical, the addition of exon skipping agents like viltolarsen may improve the quality of patients’ lives. However, data on the long-term safety and efficacy of this medication are not yet available due to its recent accelerated approval.

KEYWORDS:

• Dystrophin
• golodirsen
• accelerated approval
• viltolarsen
• exon skipping

Article highlights

• Exon skipping medications are a novel treatment for DMD patients. Four agents have been approved by the FDA in the past 7 years.

• Based on data from completed, open-label clinical trials, viltolarsen seems to be safe, effectively increasing dystrophin production and preserving motor function in DMD patients compared to external comparators (historical controls).

• Viltolarsen has been granted FDA-accelerated approval after the phase 2 clinical trials, and the drug is currently commercially available.

• Viltolarsen is currently a treatment option for DMD patients with mutations amenable for exon 53 skipping.

• A phase 3 clinical trial is still ongoing and will determine the medication’s long-term safety and efficacy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer declares that they have been directly involved in the vitolarsen program, aiding with program design, implementation, data interpretation, and publications. This review has no stock or monetary considerations directly from the NS Pharma although NS Pharma employs AGADA BioSciences for certain works on their programs – the reviewer is an executive with AGADA BioSciences in Canada. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.