Duchenne Muscular Dystrophy (DMD)

Exondys 51 (eteplirsen) is used to treat patients with Duchenne muscular dystrophy (DMD) who have a confirmed mutation in the dystrophin gene that can be treated by skipping exon 51. Exondys 51 was approved through an accelerated process that allows drugs to be approved based on a marker with suspected clinical benefits. Patients with DMD can benefit from Exondys 51 because it has the potential to increase the marker – dystrophin – in the skeletal muscle of some patients. The clinical benefits of Exondys 51 must be verified to allow the drug to be approved. In clinical trials, a shorter form of the dystrophin protein was produced in boys infused with Exondys 51 every week. Patients with DMD who are willing to receive Exondys 51 as part of their treatment plan must undergo genetic testing to confirm the mutation in their dystrophin gene and determine whether the mutation is amenable to Exondys 51 treatment. Healthcare providers administer Exondys 51 via an intravenous infusion over 35 to 60 minutes. Patients can receive intravenous infusions at the doctor’s office, home, or an infusion center. There are various factors to consider before administering Exondys 51. The dose of Exondys 51 is based on the patient’s weight. The recommended dose is 30 mg/kg body weight administered once a week.1

Clinical Pharmacology

Exon 51 of dystrophin preRNA binds to Exondys 51, leading to the exclusion of this exon during messenger RNA (mRNA) processing in patients with confirmed genetic mutations that are susceptible to exon 51 skipping. Internally truncated dystrophin proteins are produced as a result of exon skipping. In a clinical study, 36 patients were treated with Exondys 51. Through reverse transcription-polymerase chain reaction, patients were found to produce mRNA for a truncated dystrophin protein. Another study showed that after treatment with Exondys 51 for 180 weeks, the average dystrophin protein level was 0.93% of normal. A final study showed that the dystrophin level before treatment with Exondys 51 was 0.16% of normal, and it was 0.48% of normal after 48 weeks of treatment. The median increase in truncated dystrophin in the final study was 0.1%. The plasma concentration profiles of eteplirsen showed a multiphasic decline after single or multiple intravenous infusions of Exondys 51 in male children with DMD. The majority of the drug elimination occurs within 24 hours. Multiple-dose studies showed linearity and approximate dose proportionality in pharmacokinetic properties. The dose administered in the study ranged from 0.5 mg/kg/week (0.017 times the recommended dosage) to 50 mg/kg/week (1.7 times the recommended dosage).2

Get detailed prescribing information on the Exondys 51 monograph page at MPR


According to a dose-escalation study, Exondys 51 has a volume of distribution of 450 to 981 mL/kg. The mean apparent volume of distribution of Exondys 51 is 600 mL/kg at the recommended dosage of 30 mg/kg/week. Specific tissue distribution data is not yet available. Phosphorodiamidate morpholino oligomers (PMOs) do not exhibit a broad tissue distribution. According to studies conducted on mdx mice, PMOs were distributed in 6 different muscle groups. PMO distribution across the liver and kidneys is poor compared to most tissues. It is favorably cleared from circulation compared to other drugs because it is made up of neutral, water-soluble molecules.  Exondys 51 metabolism was not found to occur in the liver, which shows why PMOs are amenable to metabolic action. Exondys 51 has a plasma life of 1.62 to 3.6 hours within the 0.5 to 20 mg/kg dose range. The mean plasma half-lives of Exondys 51 administered as a single IV infusion were 3.3 hours and 3.2 hours for  doses of 30 mg/kg and 50 mg/kg, respectively. No drug accumulation of Exondys 51 was observed for varying dose schemes of 0.5 mg/kg/week to 50 mg/kg/week. The total plasma clearance of Exondys 51 varied from 233 to 615 mL/h/kg over the examined dose range. The extent of renal clearance increased with dosage. The kidneys are responsible for most of the drug’s clearance. The total clearance for Exondys 51 varied between 65% and 75%, and it occurred within the first 24 hours of drug administration.3

Read more about muscular dystrophy therapies

Exondys 51 Treatment in Patients with DMD

In a study conducted on patients with DMD, disease progression was stable for patients treated with Exondys 51 after the loss of ambulation. Initiation of the Exondys 51 treatment in patients with advanced disease progression resulted in a rapid decline in ambulatory ability before confirmatory dystrophin production. These patients experienced the loss of ambulation with relative stability on nonambulatory measures. After the loss of ambulation, upper limb functions remained stable with normal cardiac function. Sustained dystrophin production was observed after treatment with Exondys 51 on 3 complementary dystrophin assays. The duration of treatment was 180 weeks. This observational study highlighted the potential benefits of Exondys 51 in patients who were nonambulatory during treatment. With more clinical trials in progress, further clinical observations will become available to provide further evidence and context for Exondys 51 treatment in patients with DMD.4

Management of Muscle Weakness in DMD

Exondys 51 is an antisense oligonucleotide. It restores the reading frame in patients with certain mutations because it promotes exon 51 skipping in the DMD gene. It received accelerated approval from the US Food and Drug Administration (FDA) based on its ability to increase dystrophin levels in the muscle. According to the results of phase 3 clinical trials, the clinical utility of Exondys 51 is not well documented. Clinicians must make informed decisions regarding the appropriate clinical use of Exondys 51. According to clinical studies, Exondys 51 is reported to be well tolerated throughout the treatment duration. Weekly intravenous infusions of Exondys 51 can be inconvenient for patients with DMD, indicating the need for implantable venous access ports. Exondys 51 is offered to patients with confirmed mutations amenable to exon 51 skipping during diagnosis and through the stage of useful arm function. Exondys 51 is not appropriate in the late stages of DMD, and it is not expected to reverse the course of the disease. It can, however, slow the decline in muscle strength. The efficacy of Exondys 51 can be measured clinically by standardized respiratory and motor function tests. Long-term functional milestones, such as the need for respiratory support and loss of ambulation, can be used to measure the efficacy of Exondys 51 as well. The choice of motor function tests depends on the physical environment and resources available at each clinic. For example, muscle biopsy is not considered appropriate to measure the efficacy of Exondys 51 outside research studies. Additionally, a 6-minute walk distance (6MWD) is applicable in a research setting but practically, it cannot be implemented in a busy clinic with crowded hallways to measure the efficacy of Exondys 51.5


  1. Exondys 51: FAQs. Sarepta Therapeutics. Accessed August 16, 2021.
  2. Exondys 51 (eteplirsen). Package insert. Sarepta Therapeutics, Inc.; 2016. Accessed August 16, 2021.
  3. Lim KRQ, Maruyama R, Yokota T. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Des Devel Ther. 2017;11:533-545. doi:10.2147/DDDT.S97635
  4. Alfano LN, Charleston JS, Connolly AM, et al. Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy. Medicine (Baltimore). 2019;98(26):e15858. doi:10.1097/MD.0000000000015858
  5. Rivera SR, Jhamb SK, Abdel-Hamid HZ, et al. Medical management of muscle weakness in Duchenne muscular dystrophy.PLoS One. 2020;15(10):e0240687. doi:10.1371/journal.pone.0240687

Reviewed by Harshi Dhingra, MD, on 8/16/2021.