Sarepta reported that its ESSENCE Phase III confirmatory trial for two exon‑skipping antisense oligonucleotides failed to meet the primary endpoint, producing a p‑value well above the prespecified 0.05 threshold. The company attributed part of the outcome to recruitment and dosing disruptions during the COVID‑19 pandemic and said excluding pandemic‑affected participants shifted effect signals but did not reach formal statistical significance. Sarepta said it will engage the FDA to pursue full approvals based on the totality of evidence, including real‑world data accumulated during the drugs’ accelerated approvals. The therapies involved — Vyondys 53 (golodirsen) and Amondys 45 (casimersen) — are exon‑skipping ASOs intended to restore dystrophin production in defined Duchenne subpopulations; exon skipping is a genetic approach that omits faulty exons to produce truncated but functional protein. Investors reacted sharply to the miss, and industry watchers flagged the case as another test of regulators’ tolerance for biomarker‑driven approvals without clear clinical benefit.