The U.S. Food and Drug Administration 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 approval designates dordaviprone as the first systemic therapy targeted specifically at H3(K27M)–mutant DMG. Dordaviprone is an oral, brain‑penetrant imipridone that combines mitochondrial ClpP hyperactivation with D2 receptor antagonism—mechanisms demonstrated in preclinical glioma models. The FDA action offers a new regulatory pathway for a predominantly pediatric tumor where systemic options have been limited; DMG is an aggressive midline brain tumor with high unmet need.