Dordaviprone — Drug Monograph
Brand names: Modeyso
Drug class: Other
Mechanism of Action
Dordaviprone is a first-in-class, brain-penetrant oral imipridone with a dual mechanism: it is an agonist (activator) of the mitochondrial protease ClpP, driving dysregulated proteolysis of respiratory-chain subunits and mitochondrial dysfunction in tumor cells, and an antagonist of dopamine receptor D2 (DRD2). In H3 K27M-mutant diffuse midline glioma, these actions converge to impair tumor-cell metabolism and survival.
FDA Indications
- Diffuse midline glioma (DMG) harboring an H3 K27M mutation with progressive disease following prior therapy, in adult and pediatric patients 1 year of age and older (accelerated approval — first systemic therapy approved for H3 K27M-mutant DMG)
Common Side Effects
- Fatigue
- Nausea
- Vomiting
- Constipation
- Dizziness
- Decreased appetite
- Headache
- Decreased lymphocytes
Clinical Pearl
Dordaviprone is the first systemic therapy approved for H3 K27M-mutant diffuse midline glioma — a first-in-class, brain-penetrant imipridone that both activates mitochondrial ClpP and antagonizes dopamine receptor D2. Two practical points: it is dosed once weekly (not daily), and its label-defined safety monitoring centers on QTc interval prolongation (baseline/periodic ECG and electrolyte correction, avoid other QTc-prolonging drugs) plus hypersensitivity reactions and embryo-fetal toxicity.