Jazz Pharmaceuticals Receives Approval for Modeyso™ to Treat Recurrent H3 K27M-Mutant Diffuse Midline Glioma
Thursday, August 07, 2025
Jazz Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Modeyso™ (dordaviprone).
Diffuse midline glioma with H3 K27M mutation is estimated to affect approximately 2,000 people in the U.S. each year, many of whom are children and young adults. The condition is known for rapid progression and has historically lacked effective treatment options. Modeyso is expected to become commercially available in the coming weeks.
Modeyso is administered once weekly in capsule form. The FDA’s decision was based on clinical data from 50 patients with recurrent H3 K27M-mutant diffuse midline glioma across five open-label studies. The analysis showed an overall response rate of 22%, with some patients maintaining their response for over 12 months. The median duration of response was 10.3 months.
This new treatment is approved for use in adults and children aged one year and older who have recurrent diffuse midline glioma with the H3 K27M mutation, following prior therapy. The approval marks the first time a therapy has been authorised specifically for this rare and aggressive brain cancer.
The approval is conditional and may depend on results from the ongoing Phase 3 ACTION trial, which is intended to further confirm the clinical benefit of the treatment in newly diagnosed patients after radiotherapy.
The safety profile of Modeyso was assessed in 376 patients across four clinical studies. Serious adverse reactions occurred in 33% of patients. Common side effects included fatigue, headache, vomiting, nausea, and musculoskeletal pain. More serious side effects reported in a small number of cases included hydrocephalus, seizures, and muscular weakness.
Modeyso works by activating the mitochondrial caseinolytic protease P (ClpP) and inhibiting the dopamine D2 receptor (DRD2).
Laboratory tests suggest the drug triggers stress responses in tumour cells and may help restore normal function to histone proteins affected by the H3 K27M mutation.
Source: jazzpharma.com
