DIFFUSE MIDLINE GLIOMA (DMG) is an aggressive, fast-growing cancer that develops in the brain or spinal cord and has an expected survival of less than a year. “These are devastating tumors that affect children and young adults,” says Patrick Wen, a neuro-oncologist at Mass General Brigham Cancer Institute in Boston.

DMGs form in midline structures like the brain stem, which controls breathing, or the thalamus, which relays movement and sensory information. These tumors, which are diagnosed in about 200 to 400 children a year in the U.S., are typically inoperable and don’t generally respond to chemotherapy. Doctors often use radiation therapy to slow the cancer’s growth and to relieve symptoms.

On Aug. 6, 2025, the Food and Drug Administration (FDA) granted accelerated approval to a targeted therapy called Modeyso (dordaviprone) for adults and children ages 1 and older who have DMGs that have an H3 K27M mutation and that progress after treatment. Approximately 80% of DMGs carry an H3 K27M mutation.

The FDA analysis leading to the approval included five different research studies. Of the 50 people with recurrent H3 K27M-mutant DMG, 11 people who received Modeyso experienced tumor control or tumor shrinkage that lasted a median of 10.3 months.

“They took the 50 patients with measurable disease and looked at response rate, and depending on how you measured it, it ranged from a 20% to 28% response rate,” says Wen, who published a 2022 analysis of the five studies that were subsequently included in the FDA review. The brain cancer can take nine to 10 months to respond to treatment, but responses can last an average of 11 months when they do occur, according to Wen. “So, in general, patients who respond have stability for about 20 months. And this is for a disease where usually they succumb within a year.”

Chittalsinh Raulji, a pediatric neuro-oncologist at the University of Nebraska Medical Center and Children’s Nebraska in Omaha, notes that the drug’s accelerated approval was based on data that used a surrogate endpoint, a measure that is likely to predict a potential clinical benefit but also needs further study. “The drug received accelerated approval from the FDA based on its ability to shrink tumors, rather than demonstrating a clear survival benefit,” Raulji says. “This accelerated approval allows Modeyso to be used while phase III randomized trials are in progress to determine its impact on overall survival.” Wen is an investigator for a phase III trial, known as the ACTION trial, which will continue to measure progression-free survival and overall survival for people who are taking Modeyso with DMG.

The FDA approval also includes people with H3 K27M-mutant diffuse intrinsic pontine glioma (DIPG), a type of DMG that is located in the pons, a part of the brain stem that controls breathing, swallowing, balance and facial movement. DIPG, which is a cancer that primarily affects children between 5 and 10 years old, often harbors an H3 K27M mutation.

However, the FDA efficacy analysis did not include people who had DIPG because DIPG is difficult to measure, Wen says. “You can’t easily measure the shape—or tumor shrinkage—of DIPGs,” he says. “The ACTION trial that will hopefully lead to full FDA approval also excludes DIPGs. So even though they are part of the approval, the data for that group of patients are much, much less.”

Still, many children with H3 K27M-mutant DIPG could receive Modeyso as part of their care, Wen says. “But it’s important that they understand that most of the data don’t include DIPGs and temper their expectations,” he says. “Eventually, we hope there will be data from DIPGs, too.”

A safety analysis that included 376 adults and children with glioma, including those with DIPG, found that people who took Modeyso experienced fatigue, headache and musculoskeletal pain. “Nausea is a common side effect, but we can give anti-nausea medications to take care of that,” says Raulji.

This approval marks an important milestone while researchers work to find better treatments for people with DMGs, Wen says. “It’s very hard to get companies interested in developing drugs for brain tumors because they’re so hard to treat,” he says. “Hopefully this approval opens up the field a bit to more companies developing drugs. We as scientists can’t develop the drugs on our own.”