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, brain‑penetrant imipridone combines mitochondrial ClpP hyperactivation and D2 receptor antagonism and marks the first systemic therapy labeled for this genetically defined DMG subset. Regulatory documents cite trial evidence supporting tumor activity and tolerability in a population with historically dismal outcomes. Accelerated approval will likely require confirmatory studies to verify clinical benefit and durable responses in pediatric and young adult patients. DMG with H3(K27M) is an aggressive midline brain tumor driven by a specific histone mutation; the disease affects many children and young adults and has limited treatment options.