Exon skipping has the potential to help around 80% of those with Duchenne muscular dystrophy (DMD), and the therapeutic landscape is rapidly changing. At the CureDuchenne 2025 FUTURES National Conference, pharmaceutical companies offered updates and overviews on the exon-skipping therapies they are developing to treat DMD.
Exons are segments of genes that come together to form the reading frame of that gene. The DMD gene has 79 exons that can be mutated in patients with DMD, disrupting the production of functional dystrophin. Exon-skipping therapies aim to skip over the mutated exons, leading to the formation of a shortened yet still-functional version of the dystrophin protein.
All of the representatives in attendance at the session emphasized their dedication to rigorous drug testing and monitoring, not only throughout the development phases but also during clinical trials.
Sarepta Therapeutics currently has three Food and Drug Administration (FDA)-approved exon-skipping therapies to treat mutations in exons 51, 53 and 45, said Nicole LaMarca, senior director of patient affairs.
NS pharma has an FDA-approved exon 53 skipping therapy that was found to increase dystrophin production from 0.6% to 6%, on average, after 24 weeks of treatment, said Jay Chauhan.
Read more about DMD therapies
Next, Joshua Lilienstein of Avidity Biosciences discussed the company’s exon 44 skipping drug, which is in the early clinical trial stages. This treatment is designed specifically to bind to the transferrin receptor (TfR), which is found on muscle cells. The goal of this strategy, Lilienstein said, is to improve targeting, increase safety and reduce the frequency of dosing. Thus far, preliminary results have been encouraging.
Like Avidity Biosciences, Dyne Therapeutics is developing a treatment that binds to the TfR receptor, explained Chief Medical Affairs Officer Ash Dugar. Results of a clinical trial, which has enrolled patients from 4 to 16 years of age, are expected by the end of the year.
Entrada Therapeutics is currently developing therapies for mutations in exons 44, 45, 50 and 51. Their strategy is unique, Chief Corporate Affairs Officer Karla MacDonald said, as they utilize endosome escape vehicles (EEV). EEVs are a novel mode of therapeutic delivery that aim to have improved delivery and targeting.
Wave Life Sciences is currently conducting the FORWARD-53 clinical trial to evaluate its exon 53 skipping drug. “The safety profile [has] remained favorable with no drug discontinuation, and all of the patients continue to remain on the trial,” said Li-Jung Tai, Executive Medical Director of Wave Life Sciences.
Lastly, Matt Fischer of BioMarin discussed the company’s exon 51 skipping therapeutic. This drug has been designed to have improved chemical stability and exon binding. Their clinical trial is currently recruiting patients between 4 and 10 years of age who are ambulatory. The trial has sites in the United Kingdom, Spain, Italy, Turkey and the Netherlands.
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