The US Food and Drug Administration (FDA) has given accelerated approval to Jazz Pharmaceuticals for Modeyso (dordaviprone) to treat adults and paediatric patients aged one year and older with diffuse midline glioma harbouring an H3 K27M mutation, following previous therapy.
This is the first FDA-approved treatment for this rare and aggressive brain tumour.
Modeyso is expected to be commercially available in the late summer of 2025.
Continued approval may depend on verification of clinical benefit in the ongoing Phase 3 ACTION confirmatory trial, which is evaluating Modeyso's safety and clinical benefit in newly diagnosed patients with H3 K27M-mutant diffuse glioma after radiotherapy.
Modeyso is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and inhibits dopamine D2 receptor (DRD2).
In vitro, it activates the integrated stress response, induces apoptosis and alters mitochondrial metabolism, restoring histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.
This therapy was developed by Chimerix before its acquisition by Jazz in April 2025.
The FDA's decision to grant accelerated approval was based on an integrated efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma, chosen across five open-label studies.
The overall response rate (ORR) was 22%, with a median duration of response of 10.3 months. Among responders, 73% maintained their response for at least six months.
Joshua E Allen, chief scientific officer of Chimerix, a Jazz Pharmaceuticals company, stated: "The FDA approval of Modeyso is a milestone moment for the patients and families who have long needed new options, the clinicians who have tirelessly searched for solutions, and the researchers and advocates who never gave up."
Allen further added: “This approval not only equips clinicians with the first targeted option for this disease but also signals a meaningful shift in what patients and families can expect after diagnosis.”
The safety of Modeyso was evaluated in 376 patients across four open-label clinical studies. Serious adverse reactions occurred in 33% of patients, with common adverse reactions including fatigue, headache, vomiting, nausea and musculoskeletal pain.
H3 K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumour affecting midline brain and spinal cord structures. It is characterised by a specific genetic mutation disrupting epigenetic regulation and driving tumour growth. This type of glioma is most commonly diagnosed in children and young adults.
