News|Articles|September 12, 2025

Trial Data Leads to NCCN Recommendation for Modeyso in Recurrent High Grade Glioma Patients

The FDA-approved therapy is now included in National Comprehensive Cancer Network clinical guidelines as a treatment option for both pediatric and adult patients with aggressive H3 K27M-mutant diffuse gliomas, offering a new standard of care for recurrent disease.

Topline Findings

National Comprehensive Cancer Network guideline inclusion: Modeyso is now recommended as a category 2A single-agent option for pediatric and adult patients with recurrent or progressive H3 K27M-mutant diffuse glioma.

FDA accelerated approval: The therapy was approved in August 2025 based on response rates from five open-label studies, with continued approval dependent on results from the Phase III ACTION trial.

High disease burden: Gliomas account for about 25% of primary CNS tumors, affecting roughly six people per 100,000 annually in the United States, with brain tumors ranking among the top causes of cancer-related deaths in adults over 40.

Jazz Pharmaceuticals announced that Modeyso (dordaviprone) has been included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a category 2A single-agent treatment option for pediatric and adult patients with recurrent or progressive diffuse high-grade glioma harboring an H3 K27M mutation.

Modeyso received accelerated FDA approval on August 6, 2025, for patients one year and older with diffuse midline glioma exhibiting the H3 K27M mutation after progression on prior therapy, with continued approval contingent upon confirmation of clinical benefit in the ongoing Phase III ACTION trial (NCT05580562).^1,2

According to the company, its addition to both the Pediatric and Adult Central Nervous System Cancers guidelines highlights the urgent need for new options to treat this rare and aggressive brain tumor.1

How Could Modeyso Change the Treatment Landscape for Diffuse Glioma Patients?

"The rapid addition of Modeyso to the NCCN Guidelines—in both the Pediatric Central Nervous System Cancers and Central Nervous System Cancers guidelines—reflects the urgency of the unmet need that patients are faced with when diagnosed with this devastating and aggressive brain tumor," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer, Jazz Pharmaceuticals, in a press release. "We are proud to bring Modeyso to patients in the US as the first treatment option for recurrent H3 K27M-mutant diffuse midline glioma, representing a meaningful shift in the treatment landscape for patients and their families."

FDA Approval and Clinical Trial Data

The approval of Modeyso was based on pooled data from five open-label studies involving 50 patients, demonstrating an overall response rate of 22%, with a median duration of response of 10.3 months and a significant proportion of patients maintaining responses for six to twelve months.
Safety data from 376 adult and pediatric patients showed serious adverse events (AEs) in 33% of patients, with the most common AEs being fatigue, headache, vomiting, nausea, and musculoskeletal pain.¹

Epidemiology and Disease Burden

A study by the National Center for Biotechnology Information estimates that roughly six people per 100,000 in the United States are diagnosed with gliomas each year. These tumors are the most frequent type affecting the central nervous system, accounting for about a quarter of all cancer diagnoses nationwide annually.³
According to John Hopkins Medicine, approximately 33% of all brain tumors are gliomas.⁴
The National Brain Tumor Society estimates that at least one million people in the United States are currently living with a brain tumor.
Currently, the survival rate for gliomas is around 35.7%.
Approximately 81.7% of all primary brain tumors occur in the adult population.
Brain tumors rank as the seventh most frequently diagnosed type of cancer and are the sixth leading cause of cancer-related deaths in individuals aged 40 years and older.⁵

Expert Perspective

"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 an August press release, which regarded the approval. "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."2

References

Modeyso™ (dordaviprone) Included in National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for H3 K27M-mutant Diffuse Glioma. Jazz. September 9, 2025. Accessed September 11, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/modeysotm-dordaviprone-included-national-comprehensive-cancer
FDA Grants Accelerated Approval to Jazz Pharmaceuticals’ Modeyso for H3 K27M-Mutant Diffuse Midline Glioma. PharmExec. August 7, 2025. Accessed September 11, 2025. https://www.pharmexec.com/view/fda-grants-accelerated-approval-jazz-pharmaceuticals-modeyso-h3-k27m-mutant-diffuse-midline-glioma
Gliomas. NIH. Accessed September 11, 2025. https://www.ncbi.nlm.nih.gov/books/NBK441874/?utm_source=chatgpt.com
Gliomas. Hopkins Medicine. Accessed September 11, 2025. https://www.hopkinsmedicine.org/health/conditions-and-diseases/gliomas
Brain Tumor Facts. National Brain Tumor Society. Accessed September 11, 2025. https://braintumor.org/brain-tumors/about-brain-tumors/brain-tumor-facts/

Stay current in clinical research with Applied Clinical Trials, providing expert insights, regulatory updates, and practical strategies for successful clinical trial design and execution.

Subscribe Now!