FDA grants accelerated approval to dordaviprone for diffuse midline glioma

FDA accelerated approval: dordaviprone for H3 K27M–mutant diffuse midline glioma (progressed after prior therapy)

Type: Regulatory approval (accelerated approval)
Date: 2025-08-06
Agency: FDA

On August 6, 2025, the FDA granted accelerated approval to dordaviprone (Modeyso; Jazz Pharmaceuticals, Inc.), a protease activator, for adult and pediatric patients aged ≥1 year with diffuse midline glioma harboring an H3 K27M mutation, with progressive disease following prior therapy. The FDA stated this is the first FDA approval of a systemic therapy for H3 K27M–mutant diffuse midline glioma.

Evidence supporting approval

Efficacy was assessed in an integrated efficacy population (n=50) across five open-label, non-randomized U.S. trials (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], ONC018 [NCT03134131]). Patients received single-agent dordaviprone and had progressive, measurable disease per RANO-HGG criteria.

Primary endpoint: ORR by blinded independent central review using RANO 2.0.
Results: ORR 22% (95% CI, 12–36); median DOR 10.3 months (95% CI, 7.3–15.2). Among 11 responders, 73% had DOR ≥6 months and 27% had DOR ≥12 months.

Safety and labeling highlights

Label warnings/precautions include hypersensitivity, QTc prolongation, and embryo-fetal toxicity. Recommended adult dosage: 625 mg orally once weekly; pediatric dosing is weight-based (per prescribing information).

The application received priority review and included orphan drug, rare pediatric disease, and fast track designations.