IMPORTANT SAFETY INFORMATION AND INDICATIONS

IMPORTANT SAFETY INFORMATION for SCEMBLIX® (asciminib) tablets

Myelosuppression

Thrombocytopenia, neutropenia, and anemia, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX
Perform complete blood counts every 2 weeks for the first 3 months of treatment and monthly thereafter or as clinically indicated. Monitor patients for signs and symptoms of myelosuppression

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INDICATIONS

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 2 or more tyrosine kinase inhibitors (TKIs)
Ph+ CML in CP with the T315I mutation

Safety Profile

Safety Profile in Patients in Later Lines

FOR ADULTS WITH Ph+ CML-CP, PREVIOUSLY TREATED WITH ≥2 TKIs
MORE PATIENTS WERE ABLE TO STAY ON SCEMBLIX^1,2

A higher proportion of patients were still on SCEMBLIX at Week 96¹

Discontinuation rate due to adverse reactions was more than 3 times lower with SCEMBLIX vs bosutinib^1,2

6% of patients on SCEMBLIX (n=10/156) required dose reduction due to adverse reactions vs 28% on bosutinib (n=21/76)^1,3
41% of patients on SCEMBLIX (n=64/156) required dose interruption due to adverse reactions vs 58% on bosutinib (n=44/76)^1,3

Well-established tolerability profile over time¹

All-grade adverse reactions (occurring in ≥10% of patients in any treatment arm) at the Week 96 analysis¹

	SCEMBLIX (n=156)		Bosutinib (n=76)
Adverse reaction	All grades %	Grade 3 or 4 %	All grades %	Grade 3 or 4 %
URTI^a	26	0.6	12	1.3
Musculoskeletal pain^b	24	2.6	17	1.3
Headache^c	21	1.9	16	0
Fatigue^d	20	0.6	11	1.3
Rash^e	18	0.6	30	8
Hypertension^f	14	7	5	3.9
Abdominal pain^g	14	0	24	2.6
Diarrhea^h	13	0	72	11
Arthralgia	13	0.6	3.9	0
Nausea	12	0.6	46	0

Serious adverse reactions occurred in 18% of patients who received SCEMBLIX. Serious adverse reactions in ≥1% included cardiac failure congestive (1.9%), pyrexia (1.9%), urinary tract infection (1.9%), headache (1.3%), and thrombocytopenia (1.3%). Two patients (1.3%) had a fatal adverse reaction, one each for mesenteric artery thrombosis and ischemic stroke.¹

LABORATORY ABNORMALITIES

Select laboratory abnormalities (≥10%) that worsened from baseline at the Week 96 analysis¹

	SCEMBLIXⁱ		Bosutinibⁱ
Laboratory abnormality	All grades %	Grade 3 or 4 %	All grades %	Grade 3 or 4 %
Platelet count decreased	46	24	36	12
Triglycerides increased	44	5	30	2.6
Neutrophil count decreased	43	22	33	15
Hemoglobin decreased	37	2	54	5
Creatine kinase increased	30	2.6	24	5
ALT increased	26	0.6	50	16
Uric acid increased	21	6	18	2.6
AST increased	21	1.9	46	7
Lymphocyte count decreased	20	3.3	34	2.6
Phosphate decreased	18	6	20	7
Corrected Calcium decreased	16	0.6	22	0
Lipase increased	15	4.5	18	7
Creatinine increased	15	0	26	0
Amylase increased	13	1.3	13	0
ALP increased	13	0	12	0
Bilirubin increased	12	0	3.9	0
Cholesterol increased	12	0	8	0
Potassium decreased	11	0	9	0

SCEMBLIX safety data remained consistent between the Week 24 and Week 96 analyses.¹

Safety Profile in Patients With the T315I Mutation

For adults with Ph+ CML-CP with the T315I mutation

All-grade adverse reactions (in ≥10% of patients)¹	SCEMBLIX 200 mg bid (N=48)
Adverse event	All grades %	Grade 3 or 4 %
Musculoskeletal pain^j	42	4.2
Fatigue^d	31	2.1
Nausea	27	0
Rash^k	27	0
Diarrhea	21	2.1
Vomiting	19	6
Headache^l	19	2.1
Abdominal pain^m	17	8
Arthralgia	17	0
Hemorrhageⁿ	15	2.1
Cough^o	15	0
Hypertension^f	13	8
Pruritus	13	0
URTI^p	13	0
Edema	10	4.2

Select laboratory abnormalities (≥10%) that worsened from baseline¹	SCEMBLIX^q 200 mg bid
Laboratory abnormality	All grades %	Grade 3 or 4 %
ALT increased	48	6
Potassium increased	48	2.1
Lipase increased	46	21
Triglycerides increased	46	2.1
Neutrophil count decreased	44	15
Hemoglobin decreased	44	4.2
Lymphocyte count decreased	42	4.2
Phosphate decreased	40	6
Uric acid increased	40	4.2
AST increased	35	2.1
Calcium corrected decreased	33	0
Creatinine increased	31	0
Amylase increased	29	10
Platelet count decreased	25	15
Bilirubin increased	23	0
Cholesterol increased	15	0
ALP increased	13	0

Serious adverse reactions occurred in 23% of patients who received SCEMBLIX. Serious adverse reactions in >1% included abdominal pain (4.2%), vomiting (4.2%), pneumonia (4.2%), musculoskeletal pain (2.1%), headache (2.1%), hemorrhage (2.1%), constipation (2.1%), arrhythmia (2.1%), and pleural effusion (2.1%).¹

_{ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; URTI, upper respiratory tract infection.}

_{^aURTI includes: nasopharyngitis, upper respiratory tract infection, rhinitis, pharyngitis, respiratory tract infection, and pharyngotonsillitis.}

_{^bMusculoskeletal pain includes: pain in extremity, back pain, myalgia, non-cardiac chest pain, neck pain, bone pain, spinal pain, arthritis, musculoskeletal pain, and musculoskeletal chest pain.}

_{^cHeadache includes: headache and post-traumatic headache.}

_{^dFatigue includes: fatigue and asthenia.}

_{^eRash includes: rash, rash maculopapular, dermatitis acneiform, rash pustular, eczema, dermatitis, skin exfoliation, dermatitis exfoliative generalized, rash morbilliform, drug eruption, erythema multiform, and rash erythematous.}

_{^fHypertension includes: hypertension and hypertensive crisis.}

_{^gAbdominal pain includes: abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, abdominal tenderness, and epigastric discomfort.}

_{^hDiarrhea includes: diarrhea and colitis.}

_{ⁱThe denominator used to calculate the rate for SCEMBLIX and bosutinib varied from 145 to 156 and 71 to 76, respectively, based on the number of patients with a baseline value and at least one post-treatment value.}

_{^jMusculoskeletal pain includes: pain in extremity, back pain, myalgia, musculoskeletal pain, non-cardiac chest pain, bone pain, arthritis, and musculoskeletal chest pain.}

_{^kRash includes: rash, rash maculopapular, dermatitis acneiform, eczema, rash papular, skin exfoliation, and dyshidrotic eczema.}

_{^lHeadache includes: headache and migraine.}

_{^mAbdominal pain includes: abdominal pain and hepatic pain.}

_{ⁿHemorrhage includes: epistaxis, ear hemorrhage, mouth hemorrhage, postprocedural hemorrhage, skin hemorrhage, and vaginal hemorrhage.}

_{^oCough includes: cough and productive cough.}

_{^pURTI includes: upper respiratory tract infection, nasopharyngitis, rhinitis, and pharyngitis.}

_{^qThe denominator used to calculate the rate was 48 based on the number of patients with a baseline value and at least one post-treatment value.}

_{References: 1. Data on file. CABL001A2301 clinical study report. Novartis Pharmaceuticals Corp; 2022. 2. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 3. Data on file. CABL001A Week 96 SCS. Novartis Pharmaceuticals Corp; 2022.}

View the SCEMBLIX patient profiles >

Reference: 1. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.

INDICATIONS

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 2 or more tyrosine kinase inhibitors (TKIs)
Ph+ CML in CP with the T315I mutation

IMPORTANT SAFETY INFORMATION for SCEMBLIX

Myelosuppression

Thrombocytopenia, neutropenia, and anemia, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX
Perform complete blood counts every 2 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 as described in the prescribing information

Pancreatic Toxicity

Pancreatitis (including grade 3 reactions) and asymptomatic elevation in serum lipase and amylase (including grade 3/4 elevations), have occurred in patients receiving SCEMBLIX
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 as described in the prescribing information

Hypertension

Hypertension, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX
Monitor and manage hypertension using standard antihypertensive therapy during treatment with SCEMBLIX as clinically indicated
For grade 3 or higher reactions, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX as described in the prescribing information depending on persistence of hypertension

Hypersensitivity

Hypersensitivity, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX. Reactions included rash, edema, and bronchospasm
Monitor patients for signs and symptoms and initiate appropriate treatment as clinically indicated
For grade 3 or higher reactions, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX as described in the prescribing information depending on persistence of hypersensitivity

Cardiovascular Toxicity

Cardiovascular toxicity (including ischemic cardiac and central nervous system conditions; and arterial thrombotic and embolic conditions) and cardiac failure have occurred in patients receiving SCEMBLIX. Some toxicities were grade 3/4 and 3 fatalities were reported
Arrhythmia, including QTc prolongation, have occurred in patients receiving SCEMBLIX. Some of these arrhythmias were grade 3
Monitor patients with a 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 as described in the prescribing information depending on persistence of cardiovascular toxicity

Embryo-Fetal Toxicity

SCEMBLIX can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus if SCEMBLIX is used during pregnancy or if the patient becomes pregnant while taking SCEMBLIX
Verify the pregnancy status of females of reproductive potential prior to starting treatment with SCEMBLIX. Advise females to use effective contraception during treatment and for at least 1 week after the last SCEMBLIX dose

ADVERSE REACTIONS

Most common adverse reactions (≥20%) were upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea
Most common laboratory abnormalities (≥20%) were platelet count decreased, triglycerides increased, neutrophil count decreased, hemoglobin decreased, creatine kinase increased, alanine aminotransferase increased, lipase increased, amylase increased, aspartate aminotransferase increased, uric acid increased, and lymphocyte count decreased

DRUG INTERACTIONS

Asciminib is an inhibitor of CYP3A4, CYP2C9, and P-gp. Asciminib is a CYP3A4 substrate
Closely monitor for adverse reactions during concomitant use of strong CYP3A4 inhibitors and SCEMBLIX at 200 mg twice daily
Avoid concomitant use of itraconazole oral solution containing hydroxypropyl-β-cyclodextrin and SCEMBLIX at all recommended doses
Closely monitor for adverse reactions during concomitant use of certain CYP3A4 substrates and SCEMBLIX at 80 mg total daily dose. Avoid use of SCEMBLIX at 200 mg twice daily
Avoid concomitant use of CYP2C9 substrates and SCEMBLIX at all recommended doses. If coadministration with 80 mg total daily dose is unavoidable, reduce the CYP2C9 substrate dosage as recommended in its prescribing information. If coadministration with 200 mg twice daily is unavoidable, consider alternative therapy with a non-CYP2C9 substrate
Closely monitor for adverse reactions during concomitant use of certain P-gp substrates and SCEMBLIX at all recommended doses

Please see full Prescribing Information.