SCEMBLIX® (asciminib) tablets

Gafacom April 24, 2023

SCEMBLIX® (asciminib) tablets

SCEMBLIX (asciminib) is a kinase inhibitor. The chemical name of the drug substance is N-[4-(Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-3-yl)pyridine-3-carboxamidehydrogen chloride (1/1). Asciminib hydrochloride is a white to slightly yellow powder. The molecular formula of asciminib hydrochloride is C20H18ClF2N5O3.HCl, and the relative molecular mass is 486.30 g/mol for the hydrochloride salt and 449.84 g/mol for the free base.

SCEMBLIX film-coated tablets are supplied for oral use with two strengths that contain 20 mg and 40 mg of asciminib (equivalent to 21.62 mg and 43.24 mg, respectively, of asciminib hydrochloride). The tablets contain colloidal silicon dioxide, croscarmellose sodium, ferric oxide, hydroxypropyl cellulose, lactose monohydrate, lecithin, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, talc, titanium dioxide, and xanthan gum. The 20 mg tablets contain ferric oxide, yellow and ferric oxide, red. The 40 mg tablets contain ferrosoferric oxide and ferric oxide, red.

SCEMBLIX® (asciminib) tablets


INDICATIONS AND USAGE

SCEMBLIX is indicated for the treatment of adult patients with:

  • Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs).
  • Ph+ CML in CP with the T315I mutation.

Mechanism of Action

Asciminib is an ABL/BCR-ABL1 tyrosine kinase inhibitor. Asciminib inhibits the ABL1 kinase activity of the BCRABL1 fusion protein, by binding to the ABL myristoyl pocket. In studies conducted in vitro or in animal models of CML, asciminib showed activity against wild-type BCR-ABL1 and several mutant forms of the kinase, including the T315I mutation.

DOSAGE AND ADMINISTRATION

Recommended Dosage in Patients with Ph+ CML-CP, Previously Treated with Two or More TKIs

The recommended dose of SCEMBLIX 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 SCEMBLIX is taken orally without food.

Avoid food consumption for at least 2 hours before and 1 hour after taking SCEMBLIX Continue treatment with SCEMBLIX 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 SCEMBLIX is 200 mg taken orally twice daily at approximately 12-hour intervals. The recommended dose of SCEMBLIX is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking SCEMBLIX.

Missed Dose

Once Daily Dosage Regimen: If a SCEMBLIX 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 SCEMBLIX dose is missed by more than approximately 6 hours, skip the dose and take the next dose as scheduled.

Administration

Advise patients to swallow SCEMBLIX tablets whole. Do not break, crush, or chew the tablets.

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

Myelosuppression: Thrombocytopenia, neutropenia, and anemia have occurred in patients receiving SCEMBLIX.

Perform complete blood counts every two weeks for the first 3 months of treatment and monthly thereafter or as clinically indicated. Monitor patients for signs and symptoms of myelosuppression.

Based on the severity of thrombocytopenia and/or neutropenia, reduce dose, temporarily withhold, or permanently discontinue SCEMBLIX.

Pancreatic Toxicity: Assess serum lipase and amylase levels monthly during treatment with SCEMBLIX, or as clinically indicated. Monitor patients for signs and symptoms of pancreatic toxicity. Perform more frequent monitoring in patients with a history of pancreatitis. If lipase and amylase elevation are accompanied by abdominal symptoms, temporarily withhold SCEMBLIX and consider appropriate diagnostic tests to exclude pancreatitis.

Based on the severity of lipase and amylase elevation, reduce dose, temporarily withhold, or permanently discontinue SCEMBLIX.

Hypertension: Monitor and manage hypertension using standard antihypertensive therapy during treatment with SCEMBLIX as clinically indicated; for Grade 3 or higher hypertension, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending on persistence of hypertension.

Hypersensitivity: Hypersensitivity occurred in 115 of 356 (32%) patients receiving SCEMBLIX, with Grade 3 or 4 hypersensitivityreported in 6 (1.7%) patients. Reactions included rash, edema, and bronchospasm. Monitorpatients for signs and symptoms of hypersensitivity and initiate appropriate treatment as clinically indicated; for Grade 3or higher hypersensitivity, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending onpersistence of hypersensitivity.

Cardiovascular Toxicity: Monitor patients with history of cardiovascular risk factors for cardiovascular signs and symptoms. Initiate appropriate treatment as clinically indicated; for Grade 3 or higher cardiovascular toxicity, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX depending on persistence of cardiovascular toxicity.

Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, SCEMBLIX can cause fetal harm when administeredto a pregnant woman. In animal reproduction studies, administration of asciminib to pregnant rats and rabbits during theperiod organogenesis caused adverse developmental outcomes, including embryo-fetal mortality and malformations at maternal exposures (AUC) equivalent to or less than those in patients at the recommended doses. Advise pregnant womenand females of reproductive potential of the potential risk to a fetus if SCEMBLIX is used during pregnancy or if thepatient becomes pregnant while taking SCEMBLIX. Verify the pregnancy status of females of reproductive potential priorto starting treatment with SCEMBLIX. Females of reproductive potential should use effective contraception duringtreatment with SCEMBLIX and for 1 week after the last dose.

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on findings from animal studies and the mechanism of action, SCEMBLIX can cause embryo-fetal harm whenadministered to a pregnant woman.  There are no available data on SCEMBLIX use inpregnant women to evaluate a drug associated risk.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

Lactation: There are no data on the presence of asciminib or its metabolites in human milk, the effects on the breastfed child, or milkproduction.

Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with SCEMBLIX and for 1 week after the last dose.

Pediatric Use: The safety and efficacy of SCEMBLIX in pediatric patients have not been established.

Renal Impairment: No dose adjustment is required for patients with mild to severe renal impairment (estimated glomerular filtration rate[eGFR] 15 to 89 mL/min/1.73 m2) and not requiring dialysis receiving SCEMBLIX.

Hepatic Impairment: No dose adjustment is required for patients with mild [total bilirubin ≤ upper limit of normal (ULN) and aspartateaminotransferase (AST) > ULN or total bilirubin > 1 to 1.5 times ULN and any AST] to severe hepatic impairment (totalbilirubin > 3 times ULN and any AST) receiving SCEMBLIX.

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