FDA Grants Accelerated Approval For Targeted Drug for Rare Brain Tumor

The FDA has granted accelerated approval for Jazz Pharmaceuticals’ Modeyso (dordaviprone) to treat adult and pediatric patients 1 year of age and older. It is indicated for patients with a diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

Diffuse midline glioma with an H3 K27M mutation is an ultra-rare and aggressive brain tumor that affects an estimated 2,000 people in the United States each year, many of whom are children and young adults.

David F. Arons

“This approval represents a long-awaited treatment option for families affected by H3 K27M-mutant diffuse midline glioma,” David F. Arons, president and CEO of the National Brain Tumor Society, said in a news release. “This is a fast-moving, devastating disease that turns families' lives upside down. For years, this diagnosis has lacked an approved treatment and today, that changes. Families finally have a treatment option and a reason to believe in more time together to make memories that might not have otherwise been possible.”

Modeyso is the first option approved specifically for this type of cancer. It is an oral small molecule given once weekly. Modeyso is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and also inhibits the dopamine D2 receptor. In vitro, dordaviprone activates the integrated stress response, induces apoptosis, and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.

Modeyso is expected to be commercially available in the coming weeks. A company spokesperson said the wholesale acquisition cost will be available closer to launch. “With the critical patient need for a therapeutic option, we expect near-universal payer coverage from launch for this orphan indication that affects this predominantly young patient population with such a high unmet need,” the spokesperson told Formulary Watch.

Modeyso received accelerated approval based on an efficacy analysis of 50 adult and pediatric patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label clinical studies. The overall response rate was 22%. Among responders, the median duration of response was 10.3 months, with 73% maintaining their response for at least six months and 27% for at least 12 months. The response rate was assessed using Response Assessment in Neuro-Oncology (RANO) 2.0, a standard set of criteria for both high- and low-grade gliomas.

The safety of Modeyso was evaluated in 376 adult and pediatric patients with glioma across four open-label clinical studies. Serious adverse reactions occurred in 33% of patients, including hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%) and muscular weakness (2.1%). The most common adverse reactions in patients were fatigue, headache, vomiting, nausea and musculoskeletal pain

The phase 3 ACTION trial is ongoing and is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy. Company officials said this data could potentially extend Modeyso’s use to the first-line setting.

Company officials plan to hold an investor webcast on Aug. 27 at 4:30 p.m. ET to provide an overview of clinical data, patient need and commercialization strategy for Modeyso.

Modeyso was developed by Chimerix prior to its acquisition by Jazz Pharmaceuticals in April 2025 for $935 million cash. Chimerix is now a subsidiary of Jazz.