On August 6, 2025, officials with the FDA granted accelerated approval to dordaviprone (Modeyso), 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.1
This represents the first FDA approval of a systemic therapy for H3 K27M–mutant diffuse midline glioma. FDA officials noted in a statement that efficacy was evaluated in an integrated efficacy population of 50 adult and pediatric patients with recurrent H3 K27M–mutant diffuse midline glioma enrolled across 5 open-label, nonrandomized clinical trials conducted in the United States, specifically: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC016 (NCT05392374), 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/Lansky performance status 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.
Overall response rate was 22% (95% CI, 12-36), and median duration of response (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. 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.
Reference
- US Food and Drug Administration. FDA grants accelerated approval to dordaviprone for diffuse midline glioma. August 6, 2025. Accessed August 14, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma