{"entity":{"id":"dordaviprone","kind":"drug","name":"Dordaviprone","aka":[],"tldr":"Dordaviprone is the first drug ever approved for a childhood and young-adult brain tumour that had none, diffuse midline glioma with the H3 K27M mutation (August 2025).","summary":"FDA accelerated approval 6 August 2025 for patients ≥1 year with H3 K27M-mutant diffuse midline glioma progressing after prior therapy, based on an integrated analysis of 50 patients across five trials: ORR 22%, median duration of response 10.3 months. Brain-penetrant oral agent from Oncoceutics → Chimerix → Jazz Pharmaceuticals (2025). Confirmatory phase 3 ACTION trial (newly diagnosed, after radiotherapy) ongoing. Debate continues on the strength of single-arm evidence.","status":"approved","asOf":"2026-09-06","links":[{"label":"FDA approval notice","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma"},{"label":"OncLive","url":"https://www.onclive.com/view/fda-approves-dordaviprone-for-diffuse-midline-glioma"},{"label":"Arrillaga-Romany et al., ONC201 (dordaviprone) in recurrent H3 K27M-mutant diffuse midline glioma: pooled analysis behind the accelerated approval (Journal of Clinical Oncology 2024)","url":"https://doi.org/10.1200/JCO.23.01134"}],"tags":[],"related":["h3-k27m"],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["jazz"],"institutions":[],"pathways":[],"terms":["h3k27m","blood-brain-barrier","accelerated-approval"],"trials":["action-dmg"],"people":[],"bottlenecks":[],"keyPapers":["paper-arrillaga-romany-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"brand":"Modeyso","code":"ONC201","modality":"Small-molecule imipridone (ClpP agonist / DRD2 antagonist)","mechanism":"Hyperactivates the mitochondrial protease ClpP and antagonises dopamine receptor D2, triggering integrated stress response and apoptosis in H3 K27M-altered cells.","approvals":[{"region":"US","year":2025,"indication":"Recurrent H3 K27M-mutant diffuse midline glioma, age ≥1 (accelerated)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2025-08-06","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 1.1 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma","indication":"Treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy."}]},"route":"/drugs/dordaviprone/","neighbours":{"biomarker":[{"id":"h3-k27m","kind":"biomarker","name":"H3 K27M mutation","route":"/biomarkers/h3-k27m/"}],"cancer":[{"id":"brain-tumours","kind":"cancer","name":"Brain and spinal cord tumours (all types)","route":"/cancers/brain-tumours/"},{"id":"dipg-dmg","kind":"cancer","name":"Diffuse midline glioma, H3 K27-altered (including DIPG)","route":"/cancers/dipg-dmg/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"company":[{"id":"jazz","kind":"company","name":"Jazz Pharmaceuticals","route":"/companies/jazz/"}],"term":[{"id":"accelerated-approval","kind":"term","name":"Accelerated approval","route":"/terms/accelerated-approval/"},{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","route":"/terms/blood-brain-barrier/"},{"id":"h3k27m","kind":"term","name":"H3 K27M (diffuse midline glioma)","route":"/terms/h3k27m/"}],"trial":[{"id":"action-dmg","kind":"trial","name":"ACTION","route":"/trials/action-dmg/"}],"paper":[{"id":"paper-arrillaga-romany-j-clin-oncol","kind":"paper","name":"ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma","route":"/key-papers/paper-arrillaga-romany-j-clin-oncol/"}],"target":[{"id":"drd2","kind":"target","name":"Dopamine D2 receptor","route":"/targets/drd2/"},{"id":"h3-3a","kind":"target","name":"Histone H3.3 (H3-3A)","route":"/targets/h3-3a/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"idea":[{"id":"idea-bio2-paediatric-first-development","kind":"idea","name":"Develop drugs in children first when the target is a children's target","route":"/ideas/idea-bio2-paediatric-first-development/"}],"collection":[{"id":"national-brain-tumor-society","kind":"collection","name":"National Brain Tumor Society (NBTS)","route":"/collections/national-brain-tumor-society/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"}]}}