Modeyso FDA Approval History
Last updated by Judith Stewart, BPharm on Aug 7, 2025.
FDA Approved: Yes (First approved August 6, 2025)
Brand name: Modeyso
Generic name: dordaviprone
Dosage form: Capsules
Company: Jazz Pharmaceuticals plc
Treatment for: Malignant Glioma
Modeyso (dordaviprone) is a protease activator used for the treatment of diffuse midline glioma.
- Modeyso is indicated for the 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.
This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). - A glioma is brain tumor that originates from glial cells normally present in the central nervous system. The H3 K27M mutation is a specific mutation in one of the genes that encode for proteins called histone H3. The mutation is found in the majority of diffuse midline gliomas, which includes tumors located in central regions of the central nervous system such as the brainstem and thalamus.
- Modeyso contains dordaviprone, which is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptor (DRD2). In vitro, dordaviprone activates the integrated stress response, induces apoptosis, and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.
- FDA accelerated approval of Modeyso was based on a pre-specified integrated efficacy analysis of 50 adult and pediatric patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label clinical studies (ONC006, ONC013, ONC014, ONC016, and ONC018). Continued approval may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 ACTION trial (NCT05580562), which is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy.
- Modeyso capsules are administered orally once weekly on an empty stomach (at least 1 hour before or 3 hours after food intake) until disease progression or unacceptable toxicity.
- Warnings and precautions associated with Modeyso include hypersensitivity or anaphylaxis, QTc interval prolongation, and embryo-fetal toxicity.
- Common (≥20%) adverse reactions include fatigue, headache, vomiting, nausea, and musculoskeletal pain.
Common (≥2%) Grade 3 or 4 laboratory abnormalities include decreased lymphocytes, decreased calcium, and increased alanine aminotransferase.
Development timeline for Modeyso
Further information
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