Sarepta Therapeutics has announced that, following completion of the ESSENCE confirmatory study and a period of engagement with the U.S. Food and Drug Administration (FDA), it plans to submit supplemental new drug applications (sNDAs) to the FDA by the end of April 2026. These applications will seek to convert the existing accelerated approvals of AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen) into traditional, full approvals.
The FDA has confirmed that Sarepta may submit data from the ESSENCE study alongside a substantial body of published real-world evidence gathered over more than a decade of use in the Duchenne community. The adequacy of this evidence to support full approval will be subject to FDA review. Both therapies have been used to treat over 1,800 patients worldwide, from infants as young as 7 months to adults in their 30s.
What this Means & Next Steps
For families in the US living with Duchenne, the distinction between accelerated and traditional approval matters. Accelerated approval is conditional — granted on the basis of a surrogate marker (in this case, increased dystrophin production in muscle), with full approval contingent on confirming real-world clinical benefit. Traditional approval reflects the FDA’s determination that the totality of clinical and real-world evidence supports the therapy.
Sarepta is building its case on more than just the ESSENCE trial results. A decade of real-world data shows that treatment with VYONDYS 53 is associated with a 7.5-year delay in the need for night-time ventilation, while AMONDYS 45 is associated with a statistically significant slowing of lung function decline. Across Sarepta’s exon-skipping portfolio, real-world evidence points to multi-year survival benefits, delays in loss of ambulation of three to four years, and a significant reduction in emergency hospital visits.
What Is the ESSENCE Trial?
- ESSENCE (NCT02500381) is a global, Phase 3, randomised, double-blind, placebo-controlled study sponsored by Sarepta Therapeutics.
- It enrolled 225 boys with Duchenne aged 6-13, whose mutations are amenable to exon 45 or exon 53 skipping.
- ESSENCE was a global study, with trial sites spanning multiple countries across the world. The United States, Australia, and the United Kingdom were among the many locations where the study was conducted.
- Participants received either AMONDYS 45 or VYONDYS 53 (depending on their mutation), or placebo, via once-weekly intravenous infusion for up to 96 weeks
- Topline results showed numerical trends in favour of treatment over placebo, but did not reach statistical significance on the primary endpoint (the 4-step ascend velocity at 96 weeks).
- There were no new safety signals – adverse events were mostly mild to moderate and comparable between treatment and placebo groups.
- ESSENCE has now completed and is considered to have fulfilled Sarepta’s primary post-marketing requirement.
What Is AMONDYS 45?
- Generic name: Casimersen
- Who it is for: People with Duchenne whose genetic mutation is amenable to exon 45 skipping.
- How it works: AMONDYS 45 uses Sarepta’s proprietary PMO (phosphorodiamidate morpholino oligomer) chemistry to bind to exon 45 of the dystrophin gene, causing that exon to be skipped during the protein-building process. This allows the body to produce a shorter, but partially functional, form of dystrophin
- How it is given: Once-weekly intravenous infusion
- Goal: To slow muscle damage by partially restoring dystrophin, the protein absent or severely reduced in Duchenne
What Is VYONDYS 53?
- Generic name: Golodirsen
- Who it is for: People with Duchenne whose genetic mutation is amenable to exon 53 skipping.
- How it works: Using the same PMO chemistry as AMONDYS 45, VYONDYS 53 binds to exon 53 of the dystrophin gene, prompting the body to skip that section and produce a truncated but partially functional dystrophin protein.
- How it is given: Once-weekly intravenous infusion.
- Goal: To preserve remaining muscle function by partially restoring dystrophin production.
Questions or Concerns?
If any of the information in this article has raised questions or concerns, please do not hesitate to get in touch. Action Duchenne is here to support you and your family every step of the way.
Email us: Support@actionduchenne.org
