Dordaviprone

Dordaviprone is a protease activator of the mitochondrial caseinolytic protease P (ClpP). Dordaviprone also inhibits the dopamine D2 receptor.

• MODEYSO is indicated 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. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] .

• None. None.contraindicated

• Select patients for treatment with MODEYSO based on the presence of an H3 K27M mutation from tumor specimens. ( 2.1 ) • Monitor ECG and electrolytes before starting MODEYSO and periodically during treatment as clinically indicated. ( 2.2 ) • The recommended dose in adult patients is 625 mg orally once weekly. ( 2.3 ) • The recommended dose in pediatric patients weighing ≥10 kg is based on body weight (see Table 1). ( 2.3 ) • Take MODEYSO orally once weekly on an empty stomach, at least 1 hour before or 3 hours after food intake. ( 2.3 ) • Continue MODEYSO until disease progression or unacceptable toxicity. ( 2.3 ) 2.1 Patient Selection Select patients for treatment with MODEYSO based on the presence of an H3 K27M mutation from tumor specimens [see Clinical Studies ( 14 )] . An FDA-approved test for the detection of this mutation is not currently available. 2.2 Recommended Testing Before Starting MODEYSO Monitor electrocardiograms (ECG) and electrolytes before starting MODEYSO and periodically during treatment as clinically indicated [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.2 )] . 2.3 Recommended Dosage and Administration Take MODEYSO on an empty stomach, at least 1 hour before or 3 hours after food intake [see Clinical Pharmacology ( 12.3 )] . Adults The recommended dosage of MODEYSO is 625 mg orally once weekly. Pediatrics The recommended dosage of MODEYSO in pediatric patients aged 1 to <17 years who weigh at least 10 kg is based on body weight (Table 1).

• Hypersensitivity: If clinically significant hypersensitivity or anaphylaxis occur, immediately discontinue MODEYSO and initiate appropriate medical treatment and supportive care. ( 5.1 ) • QTc Interval Prolongation: MODEYSO causes concentration dependent QTc interval prolongation. Interrupt or reduce the dose of MODEYSO in patients who develop QT prolongation, and permanently discontinue MODEYSO in patients with signs of life-threatening arrhythmias. ( 5.2 , 12.2 ) • Embryo-fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Hypersensitivity MODEYSO can cause severe hypersensitivity reactions. In the pooled safety population [see Adverse Reactions ( 6.1 )], Grade 3 hypersensitivity reactions occurred in 0.3% of patients receiving MODEYSO. Signs and symptoms of hypersensitivity may include rash, hives, fever, low blood pressure, wheezing, or swelling of the face or throat. Inform patients about the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical attention if symptoms occur. If clinically significant hypersensitivity or anaphylaxis occur, immediately interrupt MODEYSO and initiate appropriate medical treatment and supportive care. Based on the severity of the adverse reaction, temporarily interrupt or permanently discontinue MODEYSO [see Dosage and Administration ( 2.4 )] .

The following potential clinically significant adverse reactions are described elsewhere in the labelling: • Hypersensitivity [see Warnings and Precautions ( 5.1 )] . • QTc Interval Prolongation [see Warnings and Precautions ( 5.2 )] . The most common (≥20%) adverse reactions are fatigue, headache, vomiting, nausea, and musculoskeletal pain. The most common (≥2%) Grade 3 or 4 laboratory abnormalities are decreased lymphocytes, decreased calcium, and increased alanine aminotransferase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chimerix at toll-free phone # 1-866-662-2679 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in WARNINGS AND PRECAUTIONS and below reflects exposure to MODEYSO at the recommended weight-based dose taken until disease progression or unacceptable toxicity in 376 adult and pediatric patients with glioma across four open-label clinical studies (ONC006, ONC013, ONC014, and ONC018) [see Clinical Studies ( 14 )] . Of the 376 patients who received MODEYSO, 35% were exposed for 6 months, and 17% were exposed for 1 year. 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% were 65 years or older.

• Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , MODEYSO can cause fetal harm when administered to a pregnant woman. There are no available data on MODEYSO use in pregnant women to inform a drug‑associated risk. In animal embryo-fetal development studies, oral administration of dordaviprone to pregnant rats and rabbits during the period of organogenesis caused embryofetal mortality, alterations to growth, and structural abnormalities at exposures below the human exposure at the highest recommended dose (see Data ). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, dordaviprone was administered orally to pregnant rats during the period of organogenesis from gestation day 7 to 17 at doses of 25, 62.5, and 125 mg/kg/day. Dordaviprone caused maternal mortality, pre-implantation loss, and embryo-fetal toxicity of absent eye and small renal papillae at the 125 mg/kg/day dose (≥2 times the human recommended doses based on body surface area).

Metabolism

Dordaviprone pharmacokinetics were predicted following a single dose in patients at the approved recommended dosage and are presented as mean (CV%) unless otherwise specified. Dordaviprone maximum concentration (C max ) is 2.8 mcg/mL (42%), and total systemic exposure (AUC) is 23 hr·mcg/mL (48%).

• Aug 6, 2025NDANDA219876Chimerix

1. 1Death2047%
2. 2Neoplasm Progression512%
3. 3Disease Progression49.3%
4. 4Hydrocephalus49.3%
5. 5Fatigue37.0%
6. 6Muscular Weakness37.0%
7. 7Nausea37.0%
8. 8Seizure37.0%
9. 9Asthenia24.7%
10. 10Csf Shunt Operation24.7%
11. 11Dyspnoea24.7%
12. 12Hospice Care24.7%
13. 13Hospitalisation24.7%
14. 14Hypoaesthesia24.7%
15. 15Malaise24.7%

The 10 most recently updated of 10 ClinicalTrials.gov registrations naming Dordaviprone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Testing for Safety and Colorectal Cancer Preventive Effects of ONC201
  Recruiting · Phase 1 · Interventional · 36 enrolled · National Cancer Institute (NCI)
  NCT05630794updated 2026-06-12
• ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant
  Completed · Phase 1 · Interventional · 20 enrolled · University of Nebraska
  NCT03932643updated 2026-05-28
• ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)
  Recruiting · Phase 3 · Interventional · 510 enrolled · Jazz Pharmaceuticals
  NCT05580562updated 2026-04-16
• Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0
  Recruiting · Phase 3 · Interventional · 433 enrolled · Gustave Roussy, Cancer Campus, Grand Paris
  NCT05476939updated 2026-02-05
• A Study of ONC201 for Refractory Meningioma
  Withdrawn · Phase 2 · Interventional · 0 enrolled · University of Nebraska
  NCT06012929updated 2026-01-26
• Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas
  Approved for marketing · Expanded access · Jazz Pharmaceuticals
  NCT04617002updated 2025-08-20
• ONC201 in Adults With Recurrent H3 K27M-mutant Glioma
  Terminated · Phase 2 · Interventional · 73 enrolled · Jazz Pharmaceuticals
  NCT03295396updated 2025-07-28
• ONC201 in Pediatric H3 K27M Gliomas
  Terminated · Phase 1 · Interventional · 134 enrolled · Jazz Pharmaceuticals
  NCT03416530updated 2025-02-14
• Oral ONC201 in Adult Recurrent Glioblastoma
  Terminated · Phase 2 · Interventional · 84 enrolled · Jazz Pharmaceuticals
  NCT02525692updated 2024-12-24
• ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer
  Terminated · Phase 2 · Interventional · 27 enrolled · Jazz Pharmaceuticals
  NCT03485729updated 2024-12-24

Frequently asked questions

How does Dordaviprone work?

Dordaviprone is a protease activator of the mitochondrial caseinolytic protease P (ClpP). Dordaviprone also inhibits the dopamine D2 receptor.

What is Dordaviprone used for?

According to FDA labeling, Dordaviprone carries indications including: MODEYSO is indicated 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. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Dordaviprone?

Dordaviprone is classified as Protease Activator, Dopamine D2 Antagonists, Protease Activators, Increased Cellular Death.

What are the brand names for Dordaviprone?

Dordaviprone is marketed under brand names including Modeyso.

What are the contraindications for Dordaviprone?

Dordaviprone labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.