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^® (asciminib) tablets 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)
- This indication is approved under accelerated approval based on major molecular response (MMR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial
Ph+ CML in CP with the T315I mutation

Safety Profile

Safety Profile in Adults With Ph+ CML-CP, Previously Treated With ≥2 TKIs

Serious adverse reactions occurred in 15% of patients who received SCEMBLIX. Serious adverse reactions in ≥1% included pyrexia (1.9%), cardiac failure congestive (1.3%), thrombocytopenia (1.3%), and urinary tract infection (1.3%). Two patients (1.3%) had a fatal adverse reaction, one each for mesenteric artery thrombosis and ischemic stroke.¹

All-grade adverse reactions (occurring in ≥10% of patients in any treatment arm)¹

	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	22	2.6	16	1.3
Headache	19	1.9	15	0
Fatigue^f	17	0.6	11	1.3
Rash^c	17	0.6	30	8
Hypertension^g	13	6	5	3.9
Nausea	12	0.6	46	0
Diarrhea^d	12	0	71	11
Arthralgia	12	0	3.9	0
Abdominal pain^e	10	0	24	2.6

Laboratory abnormalities in ADULTS with Ph+ CML-CP, previously treated with 2 OR MORE TKIs

Select laboratory abnormalities (≥10%) that worsened from baseline¹

	SCEMBLIX^h		Bosutinib^h
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	29	2.6
Neutrophil count decreased	39	17	33	13
Hemoglobin decreased	35	2	54	5
Creatine kinase increased	27	2.6	22	5
ALT increased	23	0.6	50	16
Uric acid increased	19	6	17	2.6
AST increased	19	1.9	46	7
Lymphocyte count decreased	18	2	34	2.6
Phosphate decreased	17	6	18	7
Lipase increased	14	3.9	18	7
Calcium corrected decreased	14	0.6	20	0
Creatinine increased	14	0	26	0
Amylase increased	12	1.3	13	0
Bilirubin increased	12	0	4.2	0
Cholesterol increased	11	0	8	0
Potassium decreased	10	0	9	0

Discontinuation rate due to Adverse Reactions was more than 3 times lower with SCEMBLIX vs bosutinib²

7% of patients on SCEMBLIX (n=11/156) required dose reduction due to adverse reactions vs 26% on bosutinib (n=20/76)^1,2
38% of patients on SCEMBLIX (n=60/156) required dose interruption due to adverse reactions vs 55% on bosutinib (n=42/76)^1,2

Safety Profile in 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 painⁱ	42	4.2
Fatigue^f	31	2.1
Nausea	27	0
Rash^j	27	0
Diarrhea	21	2.1
Vomiting	19	6
Headache^k	19	2.1
Abdominal pain^l	17	8
Arthralgia	17	0
Hemorrhage^m	15	2.1
Coughⁿ	15	0
Hypertension^g	13	8
Pruritus	13	0
URTI^o	13	0
Edema	10	4.2

Select laboratory abnormalities (≥10%) that worsened from baseline¹	SCEMBLIX^p 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, noncardiac chest pain, neck pain, bone pain, spinal pain, arthritis, and musculoskeletal pain.}

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

_{^dDiarrhea includes: diarrhea and colitis.}

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

_{^fFatigue includes: fatigue and asthenia.}

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

_{^hThe 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.}

_{ⁱMusculoskeletal pain includes: pain in extremity, back pain, myalgia, musculoskeletal pain, noncardiac chest pain, bone pain, arthritis, and musculoskeletal chest pain.}

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

_{^kHeadache includes: headache and migraine.}

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

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

_{ⁿCough includes: cough and productive cough.}

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

_{^pThe 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. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 2. Data on file. Week 48 Analysis Safety Set Tables. Novartis Pharmaceuticals Corp; 2021. 3. Data on file. 30 Day Safety Update. Novartis Pharmaceuticals Corp; 2021.}

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*The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Chronic Myeloid Leukemia V2.2022. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed November 19, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.

INDICATIONS

SCEMBLIX^® (asciminib) tablets 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)
- This indication is approved under accelerated approval based on major molecular response (MMR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial
Ph+ CML in CP with the T315I mutation

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
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, 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, and amylase increased

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.

Safety Profile

Safety Profile in Adults With Ph+ CML-CP, Previously Treated With ≥2 TKIs

Laboratory abnormalities in ADULTS with Ph+ CML-CP, previously treated with 2 OR MORE TKIs

Discontinuation rate due to Adverse Reactions was more than 3 times lower with SCEMBLIX vs bosutinib2

Safety Profile in Adults With Ph+ CML-CP With the T315I Mutation

Discontinuation rate due to Adverse Reactions was more than 3 times lower with SCEMBLIX vs bosutinib²