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

Bar graph of common adverse events occurring in ≥20% of patients in either treatment arm with SCEMBLIX vs bosutinib

Bar graph of common adverse events occurring in ≥20% of patients in either treatment arm with SCEMBLIX vs bosutinib

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
%

URTIa

26

0.6

12

1.3

Musculoskeletal painb

22

2.6

16

1.3

Headache

19

1.9

15

0

Fatiguef

17

0.6

11

1.3

Rashc

17

0.6

30

8

Hypertensiong

13

6

5

3.9

Nausea

12

0.6

46

0

Diarrhead

12

0

71

11

Arthralgia

12

0

3.9

0

Abdominal paine

10

0

24

2.6

 

The SCEMBLIX tolerability profile was reported based on a longer median duration of treatment compared with bosutinib

The SCEMBLIX tolerability profile was reported based on a longer median duration of treatment compared with bosutinib

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

 

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

SCEMBLIXh

Bosutinibh

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 taking SCEMBLIX discontinued treatment, compared to 25% of patients taking bosutinib

7% of patients taking SCEMBLIX discontinued treatment, compared to 25% of patients taking bosutinib

  • 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

Among patients who received SCEMBLIX, 83% were exposed for 24 weeks or longer and 67% were exposed for 48 weeks or longer

Among patients who received SCEMBLIX, 83% were exposed for 24 weeks or longer and 67% were exposed for 48 weeks or longer

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 %

Musculo​skeletal paini

42

4.2

Fatiguef

31

2.1

Nausea

27

0

Rashj

27

0

Diarrhea

21

2.1

Vomiting

19

6

Headachek

19

2.1

Abdominal painl

17

8

Arthralgia

17

0

Hemorrhagem

15

2.1

Coughn

15

0

Hypertensiong

13

8

Pruritus

13

0

URTIo

13

0

Edema

10

4.2

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

SCEMBLIXp

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.

 

Learn about SCEMBLIX dosing >

*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.