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 approval makes dordaviprone the first systemic therapy specifically approved for this mutation-defined pediatric and young-adult brain cancer. Lead sentence: FDA’s accelerated approval recognizes dordaviprone as a first-of-its-kind oral, brain-penetrant therapy combining mitochondrial ClpP hyperactivation and D2R antagonism to treat H3(K27M)–mutant DMG. The regulatory action cited clinical data supporting antitumor activity in a disease with dire unmet need. Sponsors and clinicians will now face decisions about confirmatory trials required under the accelerated pathway, patient selection for the mutation-defined indication, and considerations for pediatric dosing and safety monitoring in clinical practice and trials. The approval is drawn from recent agency documents and company-submitted clinical evidence.