National Brain Tumor Society (NBTS) welcomes the news that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to dordaviprone (Modeyso), formerly known as ONC201, as the first and only treatment for recurrent H3K27M-mutant diffuse midline glioma (DMG) — a rare, aggressive brain tumor that predominantly affects children and young adults.
This marks a milestone in the treatment landscape for one of the most devastating diagnoses a family can face. DMG patients have historically had desperately few treatment options, and this new approval offers a measure of hope and foothold for these underserved patients and their families.
“The approval of dordaviprone represents a very important step forward for patients who desperately need better treatments and a cure,” said David Arons, President and CEO of the National Brain Tumor Society. “We are especially pleased to see that dordaviprone has a duration of response that is clinically meaningful and that it is well-tolerated in such a vulnerable population. We are proud to have supported efforts to advance treatments for DMG and to see recognition of the critical unmet need in this community. We remain committed to driving cutting-edge research forward while fostering collaboration across scientific, patient and family, and regulatory communities.”
For years, NBTS has been engaged in supporting the scientific community’s efforts to understand and treat DMG – previously often known as diffuse intrinsic pontine glioma, or DIPG – for more than a decade. Our funding helped advance foundational research, and we directly supported development work on ONC201 through a grant to the drug’s previous developer. We have also worked to unite stakeholders across research, industry, and advocacy to accelerate the development of new therapies in this space.
“We hope the community can see this approval as the beginning of a new era in treatment development for DMG, and more broadly rare and recalcitrant cancers,” continued Arons. “While outcomes remain difficult for many patients, this therapy introduces a new option based on the underlying biology of the disease and patients’ biomarkers. There is much work still to be done to improve outcomes, understand which patients are most likely to benefit, and develop additional therapies.”
NBTS truly appreciates all those who were integral in the evaluation of this new therapy, including Jazz Pharmaceuticals, the Chimerix team, regulators, researchers, and, most importantly, the patients and caregivers who participated in the trial.
About the Approval
Dordaviprone’s accelerated approval is for adult and pediatric patients aged one year and older with recurrent H3K27M-mutant DMG. The basis for the approval was a reported 22% overall response rate (ORR) and durable responses were observed in a subset of patients with progressive disease following prior treatment. The company reports that, among responders, the median duration of response was 10.3 months, with 73% maintaining their response for at least six months and 27% for at least 12 months.
This approval was based on data from a pre-specified integrated efficacy analysis of 50 patients across five different open-label studies. Continued approval for this indication may be contingent on the results of a phase 3 trial already underway (ACTION Trial), which is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3K27M-mutant diffuse glioma following radiotherapy, to confirm patient benefit.
About Dordaviprone (Modyeso)
Dordaviprone, formerly known as ONC201, was developed by Oncoceutics before being acquired by Chimerix, and then recently by Jazz Pharmaceuticals in April 2025. It is a targeted therapy that is taken as an oral capsule once weekly.
About H3K27M-Mutant Diffuse Midline Glioma
H3K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumor that affects an estimated 2,000 people in the U.S. each year, many of whom are children and young adults. It is characterized by a specific genetic mutation (H3K27M) that disrupts epigenetic regulation and drives tumor growth. 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 5.1 months after progressing following frontline therapy.
