By Fineline Cube 
The U.S. Food and Drug Administration (FDA) granted accelerated approval on August 6, 2025, to dordaviprone (Modeyso, Jazz Pharmaceuticals, Inc. (NASDAQ: JAZZ) ) for adult and pediatric patients aged 1 year and older with diffuse midline glioma (DMG) harboring an H3 K27M mutation. This approval marks the first systemic therapy for patients with progressive H3 K27M-mutant DMG following prior therapy.
Mechanism of Action
Dordaviprone is a protease activator with a dual-targeting mechanism. It inhibits the dopamine receptor DRD2 and activates mitochondrial ClpP protease. This action blocks the RAS-RAF-MEK-ERK signaling pathway and activates ClpP protease within mitochondria, enabling precise targeting of cancer cells.
Clinical Trial Results
The efficacy of dordaviprone was evaluated in patients with recurrent H3 K27M-mutant DMG. The trial demonstrated an overall response rate (ORR) of 22% (95% CI: 12, 36) and a median duration of response (DOR) of 10.3 months (95% CI: 7.3, 15.2).
Safety Information
The prescribing information for dordaviprone includes warnings and precautions for hypersensitivity, QTc interval prolongation, and embryo-fetal toxicity.-Fineline Info & Tech