FDA Grants Accelerated Approval to Dordaviprone For Diffuse Midline Glioma

On August 6, 2025 the FDA granted accelerated approval to dordaviprone (Modeyso; Jazz Pharmaceuticals), for use in adult and pediatric patients with H3 K27M-mutant diffuse midline glioma and whose cancer has progressed following prior treatment. This milestone marks the first FDA-approved systematic therapy for this aggressive brain cancer.¹

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The H3 K27M mutation in diffuse midline glioma is a rare and highly fatal cancer, mostly affecting pediatric and young adult patients. Most live about 1 year after diagnosis. With disease recurrence, the survival rate is even lower. Until now, treatment options beyond radiotherapy have been limited, and systematic therapies lacked approval.¹

Clinical Data Supporting Approval

The FDA’s decision was based on pooled data from 50 adult and pediatric patients enrolled across 5 open-label US studies (ONC006 [NCT02525692], ONC13 [NCT03295396], ONC14 [NCT03416530], ONC16 [NCT05392374], ONC18 [NCT03134131]). These patients received dordaviprone (Modeyso; Jazz Pharmaceuticals) monotherapy at least 90 days after radiation. The overall response rate (ORR) was 22% with a median duration of response (DOR) of 10.3 months. Among responders, 73% maintained a response for 6 or more months, and 27% for 12 or more months.

Safety evaluations on 376 patients showed that 33% had serious adverse effects, including fluid in the brain, vomiting, headache, seizures, and muscular weakness. Common adverse effects include fatigue, headache, nausea, vomiting, and musculoskeletal pain. Labeling includes warnings of strong reactions, heart rate issues, and harm to unborn babies.

Outlook and Clinical Considerations

The FDA’s continued approval of dordaviprone (Modeyso; Jazz Pharmaceuticals) is dependent on the results of the ongoing Phase 3 ACTION trial (NC05580562). This study is evaluating dordaviprone compared with a placebo to test if it helps with a longer survival rate and stops the disease progression following standard radiotherapy.³ Adults are dosed at 625 mg orally once weekly, whereas pediatric patients receive the drug based on their body weight.² Oncology teams should begin preparing to integrate dordaviprone (Modeyso; Jazz Pharmaceuticals) into practice by assessing patient eligibility, scheduling routine interval monitoring, and keeping an eye out for hypersensitivity and risks to unborn babies.²

Conclusion

Dordaviprone’s approval offers meaningful therapeutic progress for a patient population with a historically devastating prognosis. While based on limited open-label data, the observed durable responses and manageable safety profile provide a foundation for optimism. The critical Phase 3 ACTION trial will offer further validation. As the first systemic therapy approved for H3 K27M–mutant diffuse midline glioma, Modeyso embodies an important breakthrough in neuro-oncology.

REFERENCES

1. FDA grants accelerated approval to dordaviprone. U.S. Food and Drug Administration. Published 2025. Accessed August 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dordaviprone-diffuse-midline-glioma

2. Sagonowsky E. Jazz’s Modeyso becomes first FDA-approved drug for type of aggressive brain cancer. Fierce Pharma. Published August 6, 2025. Accessed August 7, 2025. https://www.fiercepharma.com/pharma/jazzs-modeyso-becomes-first-fda-approved-drug-type-aggressive-brain-cancer

3. Jazz Pharmaceuticals Announces U.S. FDA Approval of Modeyso^TM (dordaviprone) as the First and Only Treatment for Recurrent H3 K27M-mutant Diffuse Midline Glioma | Jazz Pharmaceuticals plc. Jazz Pharmaceuticals plc. Published 2025. Accessed August 7, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-modeysotm