# Dordaviprone

Source: https://onco.cc/drugs/dordaviprone/  
OnCo record `dordaviprone` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-06
- 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: US 2025: Recurrent H3 K27M-mutant diffuse midline glioma, age ≥1 (accelerated)

## Sources

- FDA approval notice: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma
- OncLive: https://www.onclive.com/view/fda-approves-dordaviprone-for-diffuse-midline-glioma
- 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): https://doi.org/10.1200/JCO.23.01134

## Connected records

- biomarkers: [H3 K27M mutation](https://onco.cc/biomarkers/h3-k27m/)
- cancers: [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- companies: [Jazz Pharmaceuticals](https://onco.cc/companies/jazz/)
- terms: [Accelerated approval](https://onco.cc/terms/accelerated-approval/), [Blood-brain barrier (BBB)](https://onco.cc/terms/blood-brain-barrier/), [H3 K27M (diffuse midline glioma)](https://onco.cc/terms/h3k27m/)
- trials: [ACTION](https://onco.cc/trials/action-dmg/)
- key papers: [ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma](https://onco.cc/key-papers/paper-arrillaga-romany-j-clin-oncol/)
- targets: [Dopamine D2 receptor](https://onco.cc/targets/drd2/), [Histone H3.3 (H3-3A)](https://onco.cc/targets/h3-3a/)
- bottlenecks: [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- ideas: [Develop drugs in children first when the target is a children's target](https://onco.cc/ideas/idea-bio2-paediatric-first-development/)
- collections: [National Brain Tumor Society (NBTS)](https://onco.cc/collections/national-brain-tumor-society/)
- roadmaps: [Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first](https://onco.cc/roadmaps/paediatric-oncology-roadmap/)

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JSON: https://onco.cc/api/v1/entities/dordaviprone.json