Modeyso™ (dordaviprone) Included in National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for H3 K27M-mutant Diffuse Glioma

Core Insights - Jazz Pharmaceuticals has announced the commercial availability of Modeyso (dordaviprone) as the first treatment option for an ultra-rare and aggressive brain tumor, specifically for patients with recurrent or progressive diffuse high-grade glioma harboring an H3 K27M mutation [1][3]. Regulatory Approval - Modeyso received accelerated approval from the U.S. FDA on August 6, 2025, for treating adult and pediatric patients aged 1 year and older with diffuse midline glioma harboring an H3 K27M mutation [2][8]. - Continued approval is contingent upon verification of clinical benefit in the ongoing Phase 3 ACTION trial [2][8]. Clinical Guidelines - The rapid inclusion of Modeyso in the NCCN Guidelines as a category 2A treatment option highlights the urgent unmet need for patients diagnosed with this aggressive brain tumor [3]. Clinical Efficacy - An integrated efficacy analysis of 50 patients showed an overall response rate (ORR) of 22% with a median duration of response of 10.3 months [4][8]. - Among responders, 73% maintained their response for at least six months, and 27% for at least 12 months [4]. Safety Profile - The safety evaluation involved 376 patients, with serious adverse reactions occurring in 33% of cases [5][16]. - Common adverse reactions included fatigue (34%), headache (32%), and vomiting (24%) [17]. Mechanism of Action - Modeyso is an orally administered small molecule that acts as a protease activator and inhibits dopamine D2 receptor, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma [7]. Patient Demographics - H3 K27M-mutant diffuse midline glioma primarily affects children and young adults, with a median survival of approximately one year from diagnosis and less than six months after disease progression [5]. Company Overview - Jazz Pharmaceuticals is a global biopharma company focused on developing innovative medicines for serious diseases, including a growing portfolio of cancer treatments [21].