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. Dordaviprone is an oral, brain‑penetrant imipridone with dual mechanisms—mitochondrial ClpP hyperactivation and D2R antagonism—reported to exert antitumor activity in glioma models. Regulators described the approval as the first systemic therapy specifically for H3(K27M)‑mutant DMG, a high‑need indication affecting children and young adults. The approval will drive clinical uptake pressures for pediatric neuro‑oncology programs and establish an FDA precedent for targeted systemic agents in this genetically defined, aggressive tumor type.