Sarepta Therapeutics has announced top-line results from the ESSENCE trial, a global, randomized double-blind, placebo-controlled Phase 3 confirmatory study evaluating the efficacy and safety of AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen) in individuals living with Duchenne amenable to skipping exons 45 or 53, respectively.
According to Sarepta, at 96 weeks, the trial did not achieve statistical significance on the primary endpoint, the 4-step ascend velocity (Families may be more familiar with total change in 4-stair climb in seconds, whereas this is evaluating the change in speed of steps per second). ESSENCE supported favorable safety profiles for both AMONDYS 45 and VYONDYS 53 and topline results found that numerical trends favored treatment versus placebo. Additionally, when excluding trial participants whose study period overlapped with the COVID-19 pandemic (Sarepta reported 43% of COVID-19-impacted participants missed consecutive doses of exon skipping therapy), the data demonstrated a clinically meaningful slowing of disease progression.
A condition of accelerated approval is completion of a confirmatory study. The FDA may withdraw a product if there is failure to verify its clinical benefit. Sarepta indicated that the completion of the ESSENCE study is expected to fulfill the primary postmarketing requirement. The company intends to meet with the FDA to discuss converting AMONDYS 45 and VYONDYS 53 from accelerated approval to traditional approval and will submit complete ESSENCE data alongside real-world evidence in upcoming regulatory filings. We will continue to share updates with the community regarding the approval status of these therapies as information is made available.
PPMD is grateful to the families who enrolled in this trial, and to the investigators who supported them. We will continue to share updates as information becomes available.
Read Sarepta’s press release here. Read Sarepta’s community letter below:
November 3, 2025
Dear Duchenne community,
At Sarepta, we are dedicated to advancing science and therapies to serve individuals impacted by rare disease, and our mission is rooted in a deep commitment to the Duchenne community.
Clinical study update
Today, we announced topline results from ESSENCE, a global, randomized, double-blind, placebo-controlled, Phase 3 study of golodirsen and casimersen in 225 patients, ages 6 to 13 years old. The topline results, which were just announced, offer an initial view of safety and efficacy data from the study.
Gratitude and ongoing commitment
Golodirsen and casimersen were approved in 2019 and 2021, respectively, under FDA accelerated approval pathway. Completing the ESSENCE study aims to fulfill the FDA post- marketing requirement to verify the predicted clinical benefits of these therapies through a confirmatory trial.
This trial – one of the largest placebo-controlled studies ever conducted for Duchenne – spanned nearly nine years, the majority of which was spent enrolling the large number of participants across the world. The duration reflects the challenges of the ultra-rare populations eligible for this study, the unexpected constraints associated with the global pandemic, and the ethical considerations of a required 2-year placebo design in a progressively debilitating disease with unmet need.
We understand that asking families to participate in a long-term study with a required placebo control for a progressive disease is no small request, and completing the trial was possible only through the extraordinary dedication of the Duchenne community. We are deeply grateful for the courage and commitment of the families who participated in this study. Your contributions are providing valuable knowledge aimed at making a meaningful impact on patients’ lives.
With nearly a decade of real-world evidence, and the lived experience of you in the community, we remain confident in the role of exon-skipping therapies for the treatment of Duchenne.
Open exchange and transparency
We look forward to engaging with the FDA on the next steps. Our commitment to transparency and communication remains steadfast, and we will continue to provide updates as appropriate.
We know there is much more to do in Duchenne and will continue to support the community.
Sincerely,
Wendy Erler
Senior Vice President, Patient Affairs
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