The FDA granted accelerated approval to dordaviprone for diffuse midline glioma (DMG) harboring the H3(K27M) mutation in patients aged one year and older with progressive disease after prior therapy. The oral imipridone combines mitochondrial ClpP hyperactivation with D2 receptor antagonism and represents the first systemic therapy specifically approved for H3(K27M)‑mutant DMG. Regulators noted the approval addresses a population with critical unmet need, particularly pediatric and young adult patients, but required post‑approval confirmatory trials to verify clinical benefit. The product label and approved indications reflect the accelerated pathway's reliance on surrogate endpoints and limited patient populations. Pediatric oncology groups and advocates welcomed the approval while underscoring the urgency of confirmatory data and access programs for affected families.