How FDA-Approved Modeyso Works to Treat Glioma

The U.S. Food and Drug Administration (FDA) recently granted accelerated approval to Modeyso (dordaviprone) for the treatment of patients with diffuse midline glioma (a type of brain cancer) with an H3 K27M mutation.

Following the issuance of this approval, CURE sat down for an interview with Dr. Patrick Wen, director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and professor of Neurology at Harvard Medical School in Boston. Wen was the senior author of a study published in the Journal of Clinical Oncology that found monotherapy with Modeyso to be well-tolerated, with durable and clinically meaningful effectiveness among patients with recurrent H3 K27M-mutant diffuse midline glioma.

The accelerated approval is for the treatment of adult and pediatric patients aged one year and older with diffuse midline glioma harboring an H3 K27M mutation and progressive disease following prior therapy. It is, according to the regulatory agency, the first FDA-approved systemic therapy for H3 K27M-mutant diffuse midline glioma.

Wen spoke with CURE about how Modeyso works to treat glioma and, now that this treatment option is available, what unmet needs still remain for patients.

Transcript

How does Modeyso work to treat glioma, and now that it’s available, what unmet needs remain for patients?

It's thought to work in two ways. One is that it blocks some receptors, the dopamine receptors two and three. By blocking it, it slows down tumor growth. It also stimulates a different receptor that affects the metabolism of the tumor cells, and by doing so, causes the tumor cells to undergo changes that make it more likely to die. So, that's by stimulating something called ClpP and mitochondria.

Both those mechanisms are thought to be in play. It's not entirely clear which one is the more important one.

It was based on the study for measurable disease. It's mainly thalamic gliomas, which are higher up in the brain stem. We don't have as much information about the effectiveness for the diffuse intrinsic pontine glioma, which are the really devastating tumors in children.

It's really for the thalamic illness that this therapy is helpful. Hopefully it will be somewhat helpful for the DIPGs also, but we don't have as much information.

Transcript has been edited for clarity and conciseness.

References

1. “FDA grants accelerated approval to dordaviprone for diffuse midline glioma,” by the U.S. FDA. News release; Aug. 6., 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma
2. “ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma,” by Dr. Isabel Arrillaga-Romany, et al. The Journal of Clinical Oncology. May 1, 2024.
3. “FDA Approval of Modeyso ‘Important Step Forward’ For Patients with Glioma,” by Dr. Patrick Wen. CURE; Aug. 15, 2025; https://www.curetoday.com/view/fda-approval-of-modeyso-important-step-forward-for-patients-with-glioma
4. “FDA Approves Modeyso for Patients with Diffuse Midline Glioma,” by Alex Biese. CURE; Aug. 6, 2025; https://www.curetoday.com/view/fda-approves-modeyso-for-patients-with-diffuse-midline-glioma

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