Initial US Approval:
2025
Key Clinical Studies:
ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC016 (NCT05392374), and ONC018 (NCT03134131)
Drug Class/Description:
Protease activator
Indications and Usage:
MODEYSO is a protease activator 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 response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Dosage and Administration:
- Select patients for treatment with MODEYSO based on the presence of an H3 K27M mutation from tumor specimens.
- Monitor ECG and electrolytes before starting MODEYSO and periodically during treatment as clinically indicated.
- The recommended dose in adult patients is 625 mg orally once weekly.
- The recommended dose in pediatric patients weighing ≥10 kg is based on body weight.
- Take MODEYSO orally once weekly on an empty stomach (at least 1 hour before or 3 hours after food intake).
- Continue MODEYSO until disease progression or unacceptable toxicity.
Dosage Forms and Strengths:
Capsules: 125 mg
Contraindications:
None.
Warnings and Precautions:
- Hypersensitivity: If clinically significant hypersensitivity or anaphylaxis occur, immediately discontinue MODEYSO and initiate appropriate medical treatment and supportive care.
- 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.
- Embryo-fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.
Adverse Reactions:
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.
Drug Interactions:
- CYP3A4 Inhibitors: Avoid concomitant use of strong and moderate CYP3A4 inhibitors with MODEYSO. If concomitant use cannot be avoided for adults and pediatric patients who weigh at least 52.5 kg, reduce the dose of MODEYSO as recommended.
- CYP3A4 Inducers: Avoid concomitant use of strong and moderate CYP3A4 inducers with MODEYSO.
- Drugs Known to Prolong QTc Interval: Avoid concomitant use of MODEYSO with products known to prolong the QTc interval. If concomitant use cannot be avoided, separate administration of MODEYSO and the QT-prolonging product.
Use in Specific Populations:
- Lactation: Advise not to breastfeed.
Adapted From:
https://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
