FDA accelerates approval of dordaviprone-Modeyso for diffuse midline glioma

On August 6, 2025, the U.S. Food and Drug Administration (FDA) accelerated approval of the protease activator dordaviprone (dordaviprone; trade nameModeyso, developed by Jazz Pharmaceuticals, Inc.) for the treatment of patients with diffuse midline glioma 1 year old and older. These patients must carry the H3 K27M mutation and have disease progression after prior treatment. This is the first FDA approval of a systemic treatment for H3 K27M mutant diffuse midline glioma, marking an important advance in the treatment field.

The efficacy and safety of Modeyso were evaluated based on five open-label, non-randomized clinical trials (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], and ONC018 [NCT03134131]), involving a total of 50 adult and pediatric patients with recurrent H3 K27M mutant diffuse midline glioma. The efficacy assessment population included patients who had received single-agent doxorubicin and individuals assessed for disease progression and measurable disease response according to Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria.

In the study, patients must be at least 90 days post-radiotherapy, have adequate washout from previous anti-cancer therapy, have a Karnofsky Functional Status/Lansky Functional Status (KPS/LPS) score of ≥60, and have stable or reduced corticosteroid use. Patients with diffuse intrinsic pontine glioma, primary spinal tumors, and atypical histology or cerebrospinal fluid dissemination were excluded from the study.

The primary efficacy outcome measure is overall response rate (ORR) assessed by blinded independent central review (BICR) according toRANO 2.0 criteria, and the secondary outcome measure is duration of response (DOR). The results showed that the ORR was 22% (95%CI: 12, 36), and the median DOR was 10.3 months (95%CI: 7.3, 15.2). Among the 11 patients with an objective response, 73% had a DOR ≥6 months and 27% had a DOR ≥12 months.

It is worth noting that Modeyso’s prescribing information reminds you of warnings and precautions about allergic reactions, QTc interval prolongation, and embryo-fetal toxicity. For adults, the recommended oral dose is 625 mg once weekly, while for pediatric patients dose adjustment based on body weight is recommended. This information is critical to ensuring patient safety and optimizing treatment outcomes.

Reference materials:https://www.drugs.com/modeyso.html