FDA Approves Jazz Pharma’s Modeyso for Rare Brain Tumor Treatment

The US Food and Drug Administration (FDA) has granted accelerated approval to Jazz Pharmaceuticals for its treatment Modeyso (dordaviprone). This therapy is designated for adults and pediatric patients aged one year and older with diffuse midline glioma harbouring an H3 K27M mutation, following previous therapies. This marks the first FDA-approved treatment for this rare and aggressive form of brain tumor.

Modeyso is anticipated to be commercially available by the late summer of 2025. Approval for the drug is conditional and will depend on the ongoing Phase 3 ACTION confirmatory trial, which investigates its safety and clinical benefits in newly diagnosed patients with H3 K27M-mutant diffuse glioma after radiotherapy.

Modeyso’s Mechanism and Efficacy

Modeyso functions as a protease activator of the mitochondrial caseinolytic protease P (ClpP) and inhibits the dopamine D2 receptor (DRD2). Preclinical studies indicate that it activates the integrated stress response, induces apoptosis, and modifies mitochondrial metabolism, effectively restoring histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.

The FDA’s decision was based on an integrated efficacy analysis involving 50 patients with recurrent H3 K27M-mutant diffuse midline glioma across five open-label studies. The overall response rate (ORR) was recorded at 22%, with a median duration of response lasting 10.3 months. Among those who responded to treatment, 73% maintained their response for at least six months.

Joshua E. Allen, Chief Scientific Officer of Chimerix, a subsidiary of Jazz Pharmaceuticals, remarked, “The FDA approval of Modeyso is a milestone moment for the patients and families who have long needed new options, the clinicians who have tirelessly searched for solutions, and the researchers and advocates who never gave up.” He added, “This approval not only equips clinicians with the first targeted option for this disease but also signals a meaningful shift in what patients and families can expect after diagnosis.”

Safety Profile and Patient Impact

The safety of Modeyso has been assessed in a total of 376 patients across four open-label clinical studies. Serious adverse reactions were reported in 33% of patients, with common adverse effects including fatigue, headache, vomiting, nausea, and musculoskeletal pain.

Diffuse midline glioma with the H3 K27M mutation is a rare and highly aggressive brain tumor that affects midline brain and spinal cord structures. It is characterized by a specific genetic mutation that disrupts epigenetic regulation and drives tumor growth, with the highest incidence observed in children and young adults.

The FDA’s approval of Modeyso represents a significant advancement in treatment options for this challenging disease, offering hope to patients and families facing a difficult diagnosis.