Sarepta Therapeutics announced its ESSENCE Phase III confirmatory trial for two exon‑skipping antisense oligonucleotides failed to meet the study’s primary endpoint, a blow to drugs marketed under accelerated approvals. The company attributes part of the outcome to COVID‑era disruptions and missed dosing by participants during the double‑blind period. Sarepta said it plans to discuss the totality of evidence, including real‑world data accumulated during commercial accelerated‑approval use, with the FDA to pursue full approvals. The releases drove a steep selloff in Sarepta shares and intensified scrutiny of the accelerated‑approval pathway. Industry commentators highlight this as a case study in risks tied to conditional approvals that rely on biomarker surrogates and post‑approval confirmatory trials. Regulators and payers will likely revisit standards for evidentiary thresholds, particularly in rare‑disease settings where trial conduct is vulnerable to external disruptions.