Modeyso For Diffuse Midline Glioma: What's New?
- The drug dordaviprone (Modeyso) is the first systemic treatment approved specifically for a rare and aggressive brain tumor called diffuse midline glioma with a specific mutation.
- A diffuse midline glioma is an aggressive brain tumor that grows in the central structures of the brain and spreads through normal brain tissue in a web-like pattern. That makes surgery extremely difficult.
- Many of these tumors share a specific genetic change called the H3 K27M mutation, and dordaviprone (Modeyso) has been approved specifically for patients with this mutation.
- “Obviously, it’s a very needed treatment for patients who have a very aggressive, with poor survival rate or poor prognosis, tumor,” Dr. Kathryn Nevel, a neuro-oncologist at Indiana University Melvin and Bren Simon Comprehensive Cancer Center, told SurvivorNet, adding the approval is quite exciting for the field.
A new drug called dordaviprone (brand name Modeyso) is the first systemic therapy approved for a rare and aggressive brain tumor called diffuse midline glioma (DMG) harboring a specific mutation.
SurvivorNet attended the Society for NeuroOncology (SNO) Annual Meeting 2025 to discuss the exciting progress with several experts in the glioma field. While it is not a cure, it offers a real option where very few existed, and that makes a difference.
“Obviously, it’s a very needed treatment for patients who have a very aggressive, with poor survival rate or poor prognosis, tumor,” Dr. Kathryn Nevel, a neuro-oncologist at Indiana University Melvin and Bren Simon Comprehensive Cancer Center, told SurvivorNet.
“In aggressive high-grade tumors, we don’t have very many therapies that can actually make people better. So that is certainly really exciting.”
Diffuse Midline Glioma
A diffuse midline glioma is an aggressive brain tumor that grows in the central structures of the brain, such as the brainstem, thalamus, or, less commonly, the spinal cord. The word diffuse is important here. Unlike tumors that grow as a well-defined mass, these tumors spread through normal brain tissue in a web-like pattern. That makes surgery extremely difficult. In many cases, they can’t be entirely removed because doing so would damage critical parts of the brain.
For decades, this type of tumor has been one of the most devastating diagnoses in neuro-oncology. Not because doctors haven’t tried, but because of where the tumor lives and how it behaves.
The H3 K27M Mutation
Many of these tumors harbor a specific genetic change, the H3 K27M mutation. This mutation occurs in the histone H3 protein, where one small building block is swapped for another.
This mutation actively drives how aggressive the cancer is. Because of that, doctors no longer treat these tumors simply as “gliomas.” They are considered their own disease: diffuse midline glioma H3 K27M–mutant.
And for many years, this knowledge was frustrating. The mutation could be identified clearly, but we had no treatments designed to target it directly.
“In the past, we treated all gliomas pretty much the same way, but molecular testing has changed that,” Dr. Reid Thompson, Chair of Neurosurgery at Vanderbilt University Medical Center, told SurvivorNet in a previous conversation. “Now, we can identify specific mutations and tailor treatment to the individual patient.”
With molecular testing, doctors can uncover information, like the H3 K27M mutation, that can lead to more effective, targeted therapies, ultimately improving patient outcomes. We’re no longer treating gliomas as a one-size-fits-all disease.
What Is Modeyso?
Dordaviprone (brand name: Modeyso) is a prescription medicine used to treat adults and children 1 year of age and older with diffuse midline glioma that has a specific “H3 K27M” gene mutation and has gotten worse after other treatments. This approach was previously called ONC201.
“This is a very safe treatment. It’s well-tolerated. So I think that’s an excellent starting point. I think that that has particular importance for this patient population, which may suffer some of the negative consequences of [other] medications,” Dr. Rimas V. Lukas, a neuro-oncologist at the Lou & Jean Malnati Brain Tumor Institute of Northwestern University, told SurvivorNet.
Modeyso is an oral medicine taken by mouth once weekly on the same day each week. The adult dosage is 625 mg orally once weekly.
What’s The Data Show?
- The efficacy supporting this approval is based on an integrated analysis of 50 adult and pediatric patients from five open-label, non-randomized trials in the U.S.
- In that group, the overall response rate (ORR) was 22%. The partial response rate was 16% (8 people).
- The median duration of response (DOR) was 10.3 months.
Which Patients Benefit The Most?
“I think it’s a little bit difficult to understand who the optimal patients will be, as some of the patient populations that I think could have the greatest potential need for a novel therapeutic were not part of those analyses,” Dr. Lukas explained.
These studies excluded patients if they had primary spinal tumors, diffuse intrinsic pontine glioma, cerebrospinal fluid dissemination, or atypical histologies.
“Some of the most aggressive tumors were not included, and I think that’s of interest for me in the big picture,” Dr. Lukas added. “I hope that this sparks further research, which it will within the context of this medication, but also hopefully in other therapeutic approaches.”
Dr. Katie Peters, a neuro-oncologist at the Preston Robertish Brain Tumor Center at Duke University, explained that, because these tumors are very aggressive and there is a lack of available treatments, she would consider offering this drug to patients with recurrent disease who harbor the H3 K27M mutation.
“Right now, we really are in a place where if you have a target and you have a known drug with the limited options… I would try to get it for my patient at least in the recurrence setting,” she said.
In simpler terms: If someone with an H3 K27M‐mutant diffuse midline glioma has had standard treatment (usually radiation, maybe other therapies) and the tumor worsens, then dordaviprone (Modeyso) offers a chance to halt or shrink the tumor, for some patients, and for a meaningful but not unlimited interval.
It’s not a guarantee, but it’s a hopeful option that didn’t exist formally before.
