Exondys 51 (eteplirsen)

The first exon-skipping therapy approved for DMD. Targets the genetic instructions for dystrophin, skipping over the broken section (exon 51) so cells can produce a shorter but partially functional protein.

In DMD, a mutation in the dystrophin gene causes the cell's protein-making machinery to get stuck and produce no dystrophin at all. Eteplirsen tells the machinery to skip over the broken section (exon 51) and keep going. The result is a shorter-than-normal but still partially working dystrophin protein, similar to what's seen in the milder Becker muscular dystrophy.

The most common side effects in the main study were balance problems and vomiting. Allergic (hypersensitivity) reactions, including wheezing, chest pain, cough, fast heartbeat and hives, have happened during treatment. If one occurs, the care team may slow or pause the infusion. Unlike some other exon-skipping drugs, the Exondys 51 label does not list kidney toxicity as a warning or require kidney monitoring.

Given as a weekly intravenous infusion over 35-60 minutes. Typically administered at an infusion center, though home infusion may be possible after initial doses.

Yes, Eteplirsen (Exondys 51) is FDA approved (2016) for the treatment of Duchenne Muscular Dystrophy.

Eteplirsen was approved under the FDA's accelerated approval pathway based on dystrophin production in muscle biopsies from a very small number of patients, not on clinical outcomes like walking ability. The evidence of clinical benefit was limited, and an FDA advisory committee voted against approval. Janet Woodcock, director of the FDA's drug center (CDER), approved it over the objections of the review team, including the director of the Office of Drug Evaluation I, who formally appealed her decision. The advisory committee had voted 7 to 6 against accelerated approval. This decision was debated within the FDA and the broader medical community.

Eteplirsen is applicable to approximately 13% of DMD patients who have mutations amenable to exon 51 skipping. This includes patients with specific deletions in the dystrophin gene where skipping exon 51 would restore the reading frame and allow production of a shortened but partially functional dystrophin protein. Genetic testing is required to determine eligibility.

In muscle biopsies, eteplirsen increased dystrophin production to approximately 0.93% of normal levels after 180 weeks of treatment. While this is a very small amount compared to normal dystrophin levels, even small amounts of dystrophin may provide some clinical benefit. For comparison, patients with Becker muscular dystrophy (the milder form) typically have 10-40% of normal dystrophin levels.

Yes. Eteplirsen requires ongoing weekly IV infusions to maintain its effect. The drug does not permanently alter the dystrophin gene; it works by modifying how the gene's instructions are read each time the cell produces new dystrophin. If treatment is stopped, the exon-skipping effect would cease and dystrophin production would return to pre-treatment levels.

Both are made by Sarepta Therapeutics and aim to restore dystrophin, but through different approaches. Eteplirsen is an exon-skipping drug that helps the existing broken gene produce a partially functional protein, requiring weekly IV infusions indefinitely. Elevidys is a one-time gene therapy that delivers a new shortened dystrophin gene (micro-dystrophin) to muscle cells. Elevidys is approved for people aged 4 and older who can still walk and have a confirmed DMD mutation, but it cannot be used in people with a deletion in exon 8 or 9, and it now carries a boxed warning for serious liver injury and liver failure. Eteplirsen only works for people whose mutation is amenable to exon 51 skipping.