Drug Trials Snapshots: MODEYSO

MODEYSO (dordaviprone) (moh-DAY-soh) Jazz Pharmaceuticals Approval date: August 06, 2025 DRUG TRIALS SNAPSHOT SUMMARY: What is the drug for? MODEYSO is a prescription drug used for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy. How is this drug used? MODEYSO is administered as one or more capsules taken by mouth once weekly without food. Capsule contents can be opened and mixed with appropriate liquids (water, apple juice, lemonade or sports drink) and administered orally for the patients unable to swallow capsules whole. Who participated in the clinical trials? The FDA granted accelerated approval of MODEYSO based on evidence from five clinical trials (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], and ONC018 [NCT03134131]). These clinical trials enrolled both adults and children with glioma and were conducted at 68 sites in the United States. All five trials contributed to the efficacy analysis, while four of them (all except ONC016) were also used to evaluate safety. The efficacy population included 50 adult and pediatric patients with progressive and measurable diffuse midline glioma harboring an H3 K27M mutation. The median age was 31 years (range: 9 to 70), and 6% were younger than 17 years of age. Of these patients, 46% were female. By race and ethnicity, 80% were White, 6% Black or African American, 2% Asian, 10% identified as other races, 2% were unknown, and 8% were Hispanic or Latino. The safety population included 376 adult and pediatric patients who received MODEYSO at the recommended weight-based dose. The median age was 23 years (range: 3 to 80); 30% were 2 to 11 years old, 11% were 12 to 17 years old, 55% were 18 to 64 years old, and 3.7% aged 65 years or older. Of these patients, 52% were female. By race and ethnicity, 74% were White, 9% Black or African American, 4% Asian, 2.9% other or multiple races, 10% were unknown, and 13% were Hispanic or Latino. How were the trials designed? MODEYSO was evaluated in 50 adult and pediatric patients with H3 K27M-mutant diffuse midline glioma across five clinical trials. The benefit of MODEYSO was evaluated by measuring the percentage of patients who had complete, partial, or minor responses (overall response rate or ORR) assessed by blinded independent central review (BICR) according to brain tumor-specific response criteria, and by measuring the duration of that decrease in tumor size (duration of response or DOR). The side effects of MODEYSO were evaluated in 376 adult and pediatric patients with glioma across four clinical trials. DEMOGRAPHICS SNAPSHOT The efficacy population for this application included 50 patients with H3 K27M mutant diffuse midline glioma. Figure 1 summarizes the percentage of patients by sex in the efficacy population. Figure 1. Baseline Demographics by Sex, Efficacy Population Source: Adapted from FDA Review Figure 2 summarizes the percentage of patients by race in the efficacy population. Figure 2. Baseline Demographics by Race, Efficacy Population Source: Adapted from FDA Review Figure 3 summarizes the percentage of patients by age in the efficacy population. Figure 3. Baseline Demographics by Age, Efficacy Population Source: Adapted from FDA Review Figure 4 summarizes the percentage of patients by ethnicity in the efficacy population. Figure 4. Baseline Demographics by Ethnicity, Efficacy Population Source: Adapted from FDA Review The safety population for this application included 376 patients with glioma. Figure 5 summarizes how many male and female patients were included in the safety population. Figure 5. Baseline Demographics by Sex, Safety Population Source: Adapted from FDA Review Figure 6 summarizes the percentage of patients by race in the safety population. Figure 6. Baseline Demographics by Race, Safety Population Source: Adapted from FDA Review Figure 7 summarizes the percentage of patients by age in the safety population. Figure 7. Baseline Demographics by Age, Safety Population Source: Adapted from FDA Review Figure 8 summarizes the percentage of patients by ethnicity in the safety population. Figure 8. Baseline Demographics by Ethnicity, Safety Population Source: Adapted from FDA Review What are the benefits of this drug? MODEYSO was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well. In the efficacy population, 22% of patients with H3 K27M-mutant diffuse midline glioma experienced partial or minor shrinkage of their tumors; of these patients, 73% had shrinkage of their tumor that lasted more than six months. One additional patient also had tumor shrinkage when evaluated with an assessment method that factored in both corticosteroid use and performance status. Were there any differences in how well the drug worked in clinical trials among sex, race, and age? Sex: MODEYSO worked similarly in males and females. Race: The number of patients of races other than White was small; therefore, differences in how MODEYSO worked among races could not be determined. Age: There were four patients younger than 18 years and one patient older than 65 years of age in the efficacy population; therefore, differences in how MODEYSO worked among age groups could not be determined. What are the possible side effects? MODEYSO may cause serious side effects, including allergic reactions, changes in heart rhythm (QTc interval prolongation), or harm to an unborn baby. The most common side effects of MODEYSO are tiredness (fatigue); headache; vomiting; nausea; and muscle, joint, and bone pain. The most common abnormal blood tests include decreased white blood cells, decreased red blood cells, decreased calcium, and increased liver enzymes. Were there any differences in side effects among sex, race and age? Sex: The occurrence of side effects was similar in males and females. Race: The number of patients of races other than White was small; therefore, differences in the occurrence of side effects among races could not be determined. Age: The occurrence of side effects was similar across age groups. GLOSSARY CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments. COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested. EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial. PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo. SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups. PRESCRIBING INFORMATION