FDA Approves Modeyso/ONC201 for Patients with Diffuse Midline Glioma
- amanda0955
- Aug 7
- 3 min read
Updated: Aug 8
Jazz Pharmaceuticals Announces U.S. FDA Approval of Modeyso™ (dordaviprone) as the First and Only Treatment for Recurrent H3 K27M-mutant Diffuse Midline Glioma
Aug. 6, 2025 -- Jazz Pharmaceuticals plc has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Modeyso™ (dordaviprone/ONC201) for the treatment of adult and paediatric patients > 1 year of age with diffuse midline glioma (DMG) harbouring an H3 K27M mutation, with progressive disease following prior therapy.
This is a significant and historical milestone for the community, who have arguably the highest unmet need in all paediatric oncology, Modeyso is also the first therapy developed with the biological profile of the tumour in mind. For decades the diagnosis has lacked any approved treatment and this approval changes this.
The FDA's decision was based on an integrated efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma, selected from five open-label clinical studies in the US based on specified eligibility criteria. The basis for the approval was a reported 22% overall response rate (ORR) and durable responses were observed in a subset of patients with progressive disease following prior treatment. The company reports that, among responders, the median duration of response was 10.3 months, with 73% maintaining their response for at least six months and 27% for at least 12 months.
The safety of Modeyso was evaluated in 376 adult and paediatric patients with glioma across four open-label clinical studies.
Continued approval for this indication may be contingent upon the verification and description of any clinical benefit, in the Phase 3 ACTION clinical trial. (NCT05580562) currently recruiting. This is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma (DMG) following radiotherapy, but does NOT include DIPG patients.
About H3 K27M-Mutant Diffuse Midline Glioma (DMG)
H3 K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumour that primarily affects the midline structures of the brain and spinal cord. It is characterized by a specific genetic mutation (H3 K27M) that disrupts epigenetic regulation and drives tumour growth. Median survival is approximately one year from diagnosis and less than six months after progressing following frontline therapy.
About Modeyso™ (dordaviprone)
Modeyso is an orally administered small molecule given once weekly. Modeyso is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptor (DRD2). In vitro, dordaviprone/Modeyso activates the integrated stress response, induces apoptosis, and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.
Modeyso was developed by Chimerix prior to its acquisition by Jazz Pharmaceuticals in April 2025.
Modeyso (dordaviprone) is not currently approved anywhere else in the world.
Access in the UK is via a managed access program (MAP) for DIPG patients only in the absence of any available open clinical trials for the diagnosis.
UK patients with H3K27M+ DMG have access to the Phase 3 clinical trial ACTION study, which contains a placebo arm. (NCT05580562)
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