FDA Approves Dordaviprone as First and Only Treatment for Aggressive Form of Glioma

Dordaviprone (Modeyso; Jazz Pharmaceuticals) was approved today to treat recurrent H3 K27M-mutant diffuse midline glioma, an ultra-rare, aggressive brain tumor primarily affecting children and young adults, according to a press release from the company. The approval marks the first for certain patients with the rare form of glioma.

Dordaviprone is indicated for recurrent H3 K27M-mutant diffuse midline glioma, an ultra-rare, aggressive brain tumor primarily affecting children. | Image credit: wladimir1804 - stock.adobe.com

FDA granted dordaviprone accelerated approval 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, with continued approval based on outcomes in the confirmatory phase 3 ACTION trial (NCT05580562).

The approval was based on an efficacy analysis including 50 patients with recurrent H3 K27M-mutant diffuse midline glioma in 5 open-label clinical studies: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC016 (NCT05392374), and ONC018 (NCT03134131). The overall response rate in the analysis based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria was 22% (95% CI, 12%-36%) as assessed by blinded independent central review. Integrated RANO 2.0 criteria identified an additional responder.

The median duration of response was 10.3 months (95% CI, 7.3-15.2). Additionally, 73% of patients maintained their response for at least 6 months, and 27% of patients maintained their response for at least 12 months.

"This is a major turning point in neuro-oncology," Patrick Wen, MD, director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and professor of neurology at Harvard Medical School, said in a statement.1 "For the first time, we have an FDA-approved therapy for patients with recurrent H3 K27M-mutant diffuse midline glioma. While outcomes remain challenging for many patients, the objective responses observed with dordaviprone, including durable benefit in some patients, represent a meaningful advancement. This therapy was developed with the underlying biology of the tumor in mind and introduces a new treatment option for a population with historically limited choices."

The pooled analysis, which was published in the Journal of Clinical Oncology in 2024, also showed a median time to response of 8.3 months (range, 1.9-15.9) with dordaviprone.2 In addition, 7 of 15 evaluable patients had a 50% or greater corticosteroid dose reduction in the study, which translates to a rate of 46.7% (95% CI, 21.3%-73.4%).

Overall, 20% of patients experienced grade 3 treatment-related treatment-emergent adverse effects (TEAEs), with fatigue being the most common, affecting 10% of patients. There were no grade 4 treatment-related TEAEs, treatment discontinuations, or deaths reported in the study.

"This approval represents a long-awaited treatment option for families affected by H3 K27M-mutant diffuse midline glioma," David F. Arons, president and chief executive officer of the National Brain Tumor Society, said in a statement.1 "This is a fast-moving, devastating disease that turns families' lives upside down. For years, this diagnosis has lacked an approved treatment and today, that changes. Families finally have a treatment option, and a reason to believe in more time together to make memories that might not have otherwise been possible."

References

1. Jazz Pharmaceuticals announces U.S. FDA approval of Modeyso (dordaviprone) as the first and only treatment for recurrent H3K27M-mutant diffuse midline glioma. News release. Jazz Pharmaceuticals. August 6, 2025. Accessed August 6, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-modeysotm

2. Arrillaga-Romany I, Gardner SL, Odia Y, et al. ONC201 (dordaviprone) in recurrent H3 K27M-mutant diffuse midline glioma. J Clin Oncol. 2024;42(13):1542-1552. doi:10.1200/JCO.23.01134