FDA-approved antisense oligonucleotide therapies for duchenne muscular dystrophy: current status and future outlook

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder caused by dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping has emerged as a cornerstone of DMD therapy to restore dystrophin expression. This review provides a comprehensive overview of the four FDA-approved ASO therapies - eteplirsen, golodirsen, viltolarsen, and casimersen - tracing their journey from pivotal clinical trials to post-marketing updates. While the development and clinical evaluation of these agents have established a pioneering framework for rare genetic diseases, they have also highlighted critical challenges. These include complexities in clinical trial design, discrepancies between preclinical efficacy and clinical outcomes, real-world burdens, and limited patient eligibility. Furthermore, the FDA's accelerated approval of these therapies based on limited clinical data remains a subject of ongoing debate. Confirmatory trials to verify clinical efficacy and long-term follow-up studies are actively underway. Concurrently, intensive research is focused on developing next-generation ASOs to achieve enhanced therapeutic efficacy and definitive clinical outcomes. Elucidating the trajectory of research and development in this field offers profound insights for shaping future therapeutic strategies in rare diseases.