Asciminib is indicated for the treatment of adult patients with:
Asciminib is a tyrosine kinase inhibitor that targets ABL/BCR-ABL1. It works by inhibiting the ABL1 kinase activity of the BCR-ABL1 fusion protein through binding to the ABL myristoyl pocket. In both in vitro studies and animal models of chronic myeloid leukemia (CML), asciminib has demonstrated activity against the wild-type BCR-ABL1 as well as multiple mutant variants, including the T315I mutation.
At steady state, asciminib exposure (AUC and Cmax) increases slightly more than proportionally across a dose range of 10 to 200 mg (0.25 to 5 times the recommended daily dose of 80 mg), whether administered once or twice daily. Pharmacokinetic parameters are reported as geometric mean (CV%) unless otherwise specified.
Recommended Dosage in Patients with Ph+ CML-CP, Previously Treated with Two or More TKIs: The recommended dose of Asciminib is 80 mg taken orally once daily at approximately the same time each day or 40 mg twice daily at approximately 12-hour intervals. The recommended dose of Asciminib is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking Asciminib. Continue treatment with Asciminib as long as clinical benefit is observed or until unacceptable toxicity occurs.
Recommended Dosage in Patients with Ph+ CML-CP with the T315I Mutation: The recommended dose of Asciminib is 200 mg taken orally twice daily at approximately 12-hour intervals. The recommended dose of Asciminib is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking Asciminib.
Missed Dose: Once Daily Dosage Regimen: If a Asciminib dose is missed by more than approximately 12 hours, skip the dose and take the next dose as scheduled. Twice Daily Dosage Regimens: If a Asciminib dose is missed by more than approximately 6 hours, skip the dose and take the next dose as scheduled.
Dosage Modifications: Recommended Dosage Reductions for Asciminib for Adverse Reactions Dosage for Patients with CP-CML, Previously Treated with Two or More TKIs is 40 mg once daily or, 20 mg twice daily. Permanently discontinue Asciminib in patients unable to tolerate 40 mg once daily or, 20 mg twice daily. Dosage for Patients with Ph+ CML-CP with the T315I Mutation is 160 mg twice daily. Permanently discontinue Asciminib in patients unable to tolerate 160 mg twice daily.
Strong CYP3A4 Inhibitors: Asciminib is metabolized via CYP3A4. Co-administration with strong CYP3A4 inhibitors increases Asciminib Cmax and AUC, potentially raising the risk of adverse effects. Patients receiving Asciminib 200 mg twice daily along with strong CYP3A4 inhibitors should be carefully monitored for adverse reactions.
Itraconazole Oral Solution Containing Hydroxypropyl-β-cyclodextrin: Concurrent use of Asciminib with itraconazole oral solution containing hydroxypropyl-β-cyclodextrin reduces Asciminib Cmax and AUC, which may decrease its therapeutic effectiveness. Avoid using Asciminib with this formulation of itraconazole at any recommended dose.
The following clinically important adverse reactions may occur with Asciminib and are described in more detail elsewhere in the prescribing information:
Pregnancy: Animal studies and the mechanism of action indicate that Asciminib may cause harm to the embryo or fetus if administered during pregnancy. There is no clinical data on Asciminib use in pregnant women to fully assess the risk.
Lactation: It is unknown whether Asciminib or its metabolites are present in human breast milk. The effects on a breastfed child or milk production are also unknown. Due to potential serious adverse effects in the infant, women should not breastfeed during Asciminib treatment and for 1 week after the last dose. Females and Males of Reproductive Potential Based on animal studies, Asciminib may cause embryofetal harm in pregnant women.
Pregnancy Testing: Verify pregnancy status in women of reproductive potential before starting treatment with Asciminib.
Contraception: Women of reproductive potential should use effective contraception during Asciminib treatment and for 1 week after the last dose.
Infertility (Females): Animal studies suggest Asciminib may reduce fertility in females of reproductive potential. It is unknown whether this effect is reversible.
Myelosuppression: Thrombocytopenia, neutropenia, and anemia have been reported in patients treated with Asciminib. Thrombocytopenia occurred in 98 out of 356 patients (28%), with Grade 3 and Grade 4 events observed in 24 (7%) and 42 (12%) patients, respectively. The median time to first occurrence of Grade 3 or 4 thrombocytopenia was 6 weeks (range: 0.1 to 64 weeks). Among affected patients, 7 (2%) permanently discontinued Asciminib, while treatment was temporarily interrupted in 45 (13%) patients.
Pancreatic Toxicity: Pancreatitis was observed in 9 out of 356 patients (2.5%), with Grade 3 pancreatitis in 4 (1.1%) patients. All cases were reported in the Phase I (X2101) study. Two patients (0.6%) discontinued treatment permanently, and 4 (1.1%) required temporary interruption. Additionally, asymptomatic increases in serum lipase and amylase occurred in 76 patients (21%), with Grade 3 and 4 elevations in 36 (10%) and 8 (2.2%) patients, respectively. Asciminib was permanently discontinued in 7 (2%) patients due to these abnormalities.
Hypertension: Hypertension was reported in 66 out of 356 patients (19%), with Grade 3 and Grade 4 cases in 31 (9%) and 1 (0.3%) patients, respectively. The median time to onset of severe hypertension was 14 weeks (range: 0.1 to 156 weeks). Treatment was temporarily withheld in 3 (0.8%) patients due to this adverse effect.
Hypersensitivity: Hypersensitivity reactions occurred in 113 patients (32%), with Grade 3 or 4 events in 6 (1.7%) patients. These included rash, edema, and bronchospasm. Patients should be monitored for symptoms, and appropriate treatment should be initiated. For Grade 3 or higher reactions, dose interruption, reduction, or permanent discontinuation should be considered based on severity and persistence.
Cardiovascular Toxicity: Cardiovascular adverse events (including ischemic heart disease, CNS ischemia, arterial thrombosis, and embolism) were reported in 46 patients (13%), while cardiac failure occurred in 8 patients (2.2%). Grade 3 cardiovascular toxicity occurred in 12 (3.4%) patients, and Grade 3 cardiac failure in 4 (1.1%). Grade 4 cardiovascular toxicity was seen in 2 (0.6%) patients, with fatal outcomes in 3 (0.8%). Permanent discontinuation occurred in 3 (0.8%) patients due to cardiovascular toxicity and in 1 (0.3%) patient due to cardiac failure. These events were more common in patients with pre-existing cardiovascular disease, risk factors, or prior exposure to multiple TKIs.
Embryo-Fetal Toxicity: Based on animal studies and its mechanism of action, Asciminib may cause fetal harm when used during pregnancy. Studies in pregnant animals showed embryo-fetal death and malformations at exposure levels similar to or lower than those seen in humans at recommended doses. Women of reproductive potential should be advised of the risks. Pregnancy status should be confirmed before starting treatment. Effective contraception should be used during treatment and for at least 1 week after the last dose.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Geriatric Use: No significant differences in safety or efficacy were observed in patients aged 65 years or older compared to younger individuals. However, data in patients aged 75 years or older are limited.
Cytotoxic Chemotherapy
Store at or below 25°C in a cool, dry place. Protect from light and keep out of the reach of children.
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