On Aug. 6, 2025, Jazz Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Modeyso^™ (dordaviprone) for the treatment of 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the Phase 3 ACTION confirmatory trial.

Modeyso is the first and only treatment option approved by the FDA for this ultra-rare and aggressive brain tumor that affects an estimated 2,000 people in the U.S. each year, many of whom are children and young adults. The disease is characterized by rapid progression and historically has had no effective systemic treatment options.

Modeyso is administered as an oral capsule once weekly. 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 based on prespecified eligibility criteria. The overall response rate (ORR), as assessed by blinded independent central review (BICR) using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, was 22% (95% CI: 12 to 36), with an additional responder identified by integrated RANO 2.0. Among responders, the median duration of response was 10.3 months (95% CI: 7.3 to 15.2), with 73% maintaining their response for at least six months and 27% for at least 12 months.

H3 K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumor 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 tumor growth. Most commonly diagnosed in children and young adults, patients with this type of glioma often face an extremely poor prognosis, with limited therapeutic options and very low survival rates following recurrence. Median survival is approximately one year from diagnosis and less than six months after progressing following frontline therapy.

Modeyso (dordaviprone) is approved by the FDA for the treatment of 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. 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 activates the integrated stress response, induces apoptosis, and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.