On August 6, 2025, the Food and Drug Administration granted accelerated approval to dordaviprone (Modeyso, Jazz Pharmaceuticals, Inc.), a protease activator, for 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 represents the first FDA approval of a systemic therapy for H3 K27M-mutant diffuse midline glioma.
Full prescribing information for Modeyso will be posted on Drugs@FDA.
Efficacy and Safety
Efficacy was evaluated in an integrated efficacy population of 50 adult and pediatric patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label, non-randomized clinical trials conducted in the U.S. (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], and ONC018 [NCT03134131]). The efficacy population comprised patients who received single-agent dordaviprone for diffuse midline glioma harboring an H3 K27M mutation and had progressive and measurable disease per Response Assessment in Neuro-Oncology-High Grade Glioma (RANO-HGG) criteria.
Patients were also at least 90 days post radiation therapy, had an adequate washout period from prior anticancer therapies, a Karnofsky Performance Status/Lansky Performance Status (KPS/LPS) score ≥60, and stable or decreasing corticosteroid use. Patients with diffuse intrinsic pontine glioma, primary spinal tumors, atypical histologies, or cerebrospinal fluid dissemination were excluded.
The major efficacy outcome measure was overall response rate (ORR) assessed by blinded independent central review (BICR) according to RANO 2.0 criteria, with duration of response (DOR) as a secondary outcome measure. ORR was 22% (95% CI: 12, 36) and median DOR was 10.3 months (95% CI: 7.3, 15.2). Among the 11 patients with objective responses, 73% had a DOR of ≥ 6 months and 27% had a DOR of ≥ 12 months.
The dordaviprone prescribing information includes warnings and precautions for hypersensitivity, QTc interval prolongation, and embryo-fetal toxicity.
Recommended Dosage
For adults, the recommended dordaviprone dosage is 625 mg orally once weekly. For pediatric patients, the recommended dosage is based on body weight. See the prescribing information for more information.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. Dordaviprone received orphan drug designation, rare pediatric disease designation, and fast track designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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