MODEYSO

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE 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 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 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. ( 1 ) This indication is approved under accelerated approval based on response rate and duration of response [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Dosage and administration 2 DOSAGE AND ADMINISTRATION • 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 500 ms or An increase of >60 ms from baseline Interrupt MODEYSO until QTc interval ≤480 ms or return to baseline. Resume MODEYSO at the next lower dose level. Torsades de pointes, polymorphic ventricular tachycardia or signs or symptoms of serious or life-threatening arrhythmia Permanently discontinue MODEYSO. Other Adverse Reactions [see Adverse Reactions ( 6.1 )] Grade 3 or 4 Interrupt MODEYSO until ≤Grade 1 or return to baseline. Resume MODEYSO at the next lower dose level. Recurrent Grade 4 Permanently discontinue MODEYSO. a. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. b. See Table 2 for recommended dosage reductions. 2.5 Dosage Modifications for CYP3A4 Inhibitors Avoid concomitant use of strong and moderate CYP3A4 inhibitors with MODEYSO. • If concomitant use of a strong CYP3A4 inhibitor cannot be avoided for adult and pediatric patients who weigh at least 52.5 kg, reduce the dose of MODEYSO from 625 mg to 375 mg once weekly. • If concomitant use of a moderate CYP3A4 inhibitor cannot be avoided for adult and pediatric patients who weigh at least 52.5 kg, reduce the dose of MODEYSO from 625 mg to 500 mg once weekly. • The recommended dosage for pediatric patients weighing less than 52.5 kg who are receiving strong or moderate CYP3A4 inhibitors has not been established. Upon discontinuation of the CYP3A4 inhibitor, wait for 3 to 5 plasma half-lives of the CYP3A4 inhibitor, then increase MODEYSO to the dose that was taken before starting the CYP3A4 inhibitor [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )]. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • 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 pa