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Pharmaceutical Breakthrough for the Treatment of Duchenne Muscular Dystrophy

By: Rubab Hassan, PharmD Candidate c/o 2022

             Duchenne muscular dystrophy (DMD) is a genetic disorder that causes muscle degeneration and weakness along with various other symptoms. It is predominantly caused by deletions of one or more exons, which lead to mutations of the dystrophin gene. Dystrophin stops muscle fibers from being degraded by proteases. Therefore, the loss of dystrophin in the body will allow muscle to be broken down, causing a multitude of health complications in patients who have DMD. 1 DMD is a rare disease, which is why viltolarsen (Viltepso™), one of the newest FDA approved treatments for DMD, is such a breakthrough. 2

DMD affects 1 out of every 3,600 male infants worldwide and in very rare cases it can affect females. Patients with this disease usually only live until their twenties or thirties. It is an X-linked recessive allelic disorder that causes the deletion of exons resulting in unstable mRNA. This results in the production of extremely short dystrophin molecules that are degraded very quickly and lead to severe muscular dystrophy. The absence of dystrophin in patients with DMD leads to muscle membrane damage, leakage of creatinine kinase, and the replacement of muscle tissue with fat tissue. This can then lead to respiratory problems and cardiomyopathy, which has been the leading cause of the shortened lifespans of those who suffer from DMD. 2 Viltolarsen is an antisense phosphorodiamidate morpholino oligonucleotide that aims to bind to a region in exon 53 of the DMD gene pre-mRNA and prevent it from being included in the mature mRNA before translation. This technique is called exon skipping, where the goal is to mask the space where the deleted exon would be so that it is ignored during protein production. With the defective genetic material gone, the translation can carry on as normal and tell the body to produce more dystrophin. 3

Viltolarsen was approved under the FDA’s accelerated approval pathway, which looks at drugs that have great potential of providing clinical benefit for life-threatening disease states. 2 Even though the process is accelerated, the FDA takes into account the well-controlled studies that have verified the potential clinical benefits of the drugs. Further research is always needed to fully comprehend the magnitude of the potential and how beneficial the drug really is. This program allows drugs indicated for these diseases to be available to patients faster so that they can benefit from them as soon as possible. The significance of this is that since pharmaceutical breakthroughs are rare for diseases like DMD, it’s crucial that patients get access to it as soon as possible to optimize the outcome. It is difficult to come across such breakthroughs due to a variety of reasons, such as the lack of understanding of rare diseases and the small population of patients that can participate in clinical trials that do aim to find treatments for these diseases. 4 The FDA’s accelerated approval pathway is one way of overcoming these barriers and trying to do justice to all of patients out there who struggle with these diseases.

A study called “Safety and Dose Finding Study of NS-065/NCNP-01 in Boys with Duchenne Muscular Dystrophy” looked at the efficacy of viltolarsen in DMD patients with the mutation that can be altered with exon 53 skipping. This was a multicenter, 2-period, dose-finding study. In the first 4 weeks of this study, Period 1, the patients were randomly given either weekly IV infusions of viltolarsen 40mg/kg or the placebo. After the initial four weeks, Period 2 began and the patients were randomized once again and given weekly IV infusions of either 40 mg/kg or 80 mg/kg of viltolarsen once weekly from weeks 5-24. 5 The primary efficacy endpoint was the change from baseline in dystrophin levels at week 25. The results of this study showed that in the patients who received viltolarsen 80 mg/kg once weekly, mean dystrophin levels had increased from a baseline of 0.6% of normal to 5.9% of normal (SD 4.5). The mean change in dystrophin levels was 5.3% (p=0.01). This analysis was done with a Western blot, which was normalized to myosin heavy chain. 6 Even though the numbers may seem small, any enhancement in the amount of dystrophin can improve the prognosis for patients with DMD.

The FDA approved dose of viltolarsen is 80 mg/kg once weekly given as a 60-minute IV infusion. Based on what was found in animal studies, kidney toxicity is a potential adverse event. The most common adverse events experienced by patients were upper respiratory tract infections, injection site reactions, and pyrexia. 6 There is not as much data on the safety of this drug because of the accelerated approval, but studies are being done to further evaluate the safety outcomes.

As advocates for quality pharmacotherapy and access to care, pharmacists should be aware of rare disease states and get more involved in their drug therapy. These patients should know know that they are not forgotten and that their lives are just as valuable as anyone else’s.


  1. Darras B. Duchenne and Becker muscular dystrophy: Clinical features and diagnosis. UpToDate.  https://www.uptodate.com/contents/duchenne-and-becker-muscular-dystrophy-clinical-features-and-diagnosis. Last Updated 07/24/2020.
  2. FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation. Published 08/12/2020.
  3. Viltolarsen – DrugBank. https://www.drugbank.ca/drugs/DB15005. Accessed 09/14/2020.
  4. Rare Diseases at FDA. U.S. Food and Drug Administration. https://www.fda.gov/patients/rare-diseases-fda. Accessed 01/21/2021
  5. Safety and Dose Finding Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD) – Full Text View. Full Text View – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02740972. Accessed September 26, 2020.
  6. Viltepso (Viltolarsen) [package insert]. Paramus, NJ; NS Pharma, Inc.; Revised 08/2020.
  7. VILTEPSO (viltolarsen) for the Treatment of Duchenne Muscular. https://www.clinicaltrialsarena.com/projects/viltepso-viltolarsen. Accessed 09/14/2020.
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