Topline Findings
- FDA approval milestone: Modeyso (dordaviprone) is the first and only treatment approved for recurrent H3 K27M-mutant diffuse midline glioma in patients aged one year and older.
- Promising clinical outcomes: Integrated trial data showed a 22% objective response rate with a median response duration of 10.3 months.
- High unmet medical need addressed: The approval of Modeyso offers new hope for pediatric and young adult patients with this aggressive brain tumor who previously had no effective treatment options.
The FDA has granted accelerated approval to Jazz Pharmaceuticals’ Modeyso (dordaviprone), marking the first and only approved treatment for recurrent H3 K27M-mutant diffuse midline glioma in patients aged one year and older. According to the company, continued approval is contingent on results from the ongoing Phase III ACTION trial (NCT05580562).1,2
What does FDA Approval of Modeyso mean for Patients with H3 K27M-Mutant Diffuse Midline Glioma?
"This is a major turning point in neuro-oncology," said Patrick Wen, MD, director, center for neuro-oncology, Dana-Farber Cancer Institute, professor of neurology, Harvard Medical School, in a press release. "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."
Phase II Efficacy and Safety Data
- The efficacy and safety of Modeyso were evaluated across five open-label, non-randomized Phase II trials: ONC006, ONC013, ONC014, ONC016, and ONC018.
- A planned analysis combined data from 50 patients with recurrent H3 K27M-mutant diffuse midline glioma who had tumors that could be measured using Response Assessment in Neuro-Oncology (RANO) criteria.
- Tumor responses were evaluated every eight weeks by blinded independent central review.
- The primary endpoint of each trial was objective response rate (ORR), while safety was assessed in 376 adult and pediatric patients across four of the trials.
- Results from an integrated efficacy analysis of 50 patients selected from the trials showed an ORR of 22% based on RANO.
- 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.
- Serious adverse events (SAEs) were reported in 33% of patients. SAEs that were reported in at least 2% of patients included hydrocephalus, vomiting, headache, seizure, and muscular weakness.
- The most common AEs included fatigue, headache, vomiting, nausea and musculoskeletal pain.1
Expert and Industry Reactions
"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," said Joshua E. Allen, PhD, chief scientific officer, Chimerix, a Jazz Pharmaceuticals Company, in the press release. "We're proud to deliver precisely the kind of transformative innovation we strive for, and we congratulate our combined Chimerix and Jazz team, and the community who worked together tirelessly to bring this treatment forward. 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. We would like to extend our thanks to the patients, advocates, clinicians, principal investigators, scientists, regulators and partner institutions who made this possible."
Glioma Prevalence
According to a study published in The National Center for Biotechnology Information, there are approximately six cases of gliomas diagnosed per every 100,000 people in the United States. Gliomas are considered the most common tumors of the central nervous system, representing 25% of all tumors diagnosed in the United States annually.3
Patient Advocacy Perspective
"This approval represents a long-awaited treatment option for families affected by H3 K27M-mutant diffuse midline glioma," said David F. Arons, president, CEO, National Brain Tumor Society, in the press release. "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
- Jazz Pharmaceuticals Announces U.S. FDA Approval of Modeyso™ (dordaviprone) as the First and Only Treatment for Recurrent H3 K27M-mutant Diffuse Midline Glioma. Jazz. August 6, 2025. Accessed August 7, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-modeysotm
- ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION). Clinicaltrials.gov. Accessed August 7, 2025. https://clinicaltrials.gov/study/NCT05580562?utm_source=chatgpt.com
- Gliomas. NIH. Accessed August 7, 2025. https://www.ncbi.nlm.nih.gov/books/NBK441874/?utm_source=chatgpt.com
