FDA Grants Accelerated Approval to Jazz’s Dordaviprone (Modeyso), the First Treatment for Ultra-Rare Brain Tumor

The FDA granted accelerated approval to Jazz Pharmaceuticals' dordaviprone (Modeyso) for patients aged 1 year and older with recurrent H3 K27M-mutant diffuse midline glioma, an ultra-rare and aggressive brain tumor primarily affecting children and young adults254.

This marks the first approved systemic treatment specifically for H3 K27M-mutant diffuse midline glioma4.

Approval was based on a pooled analysis of 50 patients in phase 1/2 trials, with an overall response rate (ORR) of 22% and median duration of response (mDOR) of 10.3 months35.

The drug received multiple FDA designations:
orphan drug, rare pediatric disease, fast track, and priority review, underscoring the high unmet medical need1.

Dordaviprone's mechanism involves dual action as a mitochondrial ClpP agonist and dopamine D2 receptor antagonist, inducing selective apoptosis in H3 K27M-mutant glioma cells1.

Adverse event warnings include risk for hypersensitivity reactions, QTc prolongation (potential effect on heart rhythm), and embryo-fetal toxicity; regular monitoring is recommended13.

Continued approval depends on confirmatory results from the phase 3 ACTION trial, with the first interim analysis expected by the end of 2025 and ongoing enrollment35.

Modeyso is to be launched commercially in the coming weeks, with more details expected in late August 20253.

Sources:

1. https://www.targetedonc.com/view/dordaviprone-receives-accelerated-fda-approval-for-diffuse-midline-glioma

2. https://www.fiercepharma.com/pharma/jazzs-modeyso-becomes-first-fda-approved-drug-type-aggressive-brain-cancer

3. https://www.oncologypipeline.com/apexonco/jazz-gets-its-chimerix-approval

4. https://firstwordpharma.com/story/5986969

5. https://www.ajmc.com/view/fda-approves-dordaviprone-as-first-and-only-treatment-for-aggressive-form-of-glioma