NCCN Guidelines Add Jazz’s Modeyso™ As A Category 2A Option For H3 K27M-Mutant Diffuse Glioma

Jazz Pharmaceuticals plc announced that Modeyso™ (dordaviprone) has been included in the 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 harbouring an H3 K27M mutation. This recognition comes shortly after the FDA granted accelerated approval on August 6, 202,5 for the same patient population aged 1 year and older. Continued approval is subject to confirmatory results from the ongoing Phase 3 ACTION trial.

The FDA decision was based on data from an integrated analysis of 50 patients across five open-label studies. Modeyso achieved an overall response rate (ORR) of 22% (95% CI: 12–36), with responses lasting a median of 10.3 months. Among these, 73% of responders maintained benefit for at least 6 months, and 27% for at least 12 months, underscoring its potential as a much-needed treatment option for this aggressive and rare cancer.

"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 tumour. We are proud to bring Modeyso to patients in the U.S. 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," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer of Jazz Pharmaceuticals. 

Safety findings were consistent across studies, with data from 376 adult and pediatric patients with glioma. Serious adverse reactions occurred in 33%, most commonly hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizures (2.4%), and muscular weakness (2.1%). The most frequent adverse events (≥20%) were fatigue, headache, vomiting, nausea, and musculoskeletal pain. Inclusion in the NCCN Guidelines further reinforces the clinical relevance of Modeyso while Phase 3 data are awaited.