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 SCEMBLIX1,2

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

Proportion of patients still on treatment at the 96-week analysis. SCEMBLIX 54%, Bosutinib 20%

Proportion of patients still on treatment at the 96-week analysis. SCEMBLIX 54%, Bosutinib 20%

 

Discontinuation rate due to adverse reactions was more than 3 times lower with SCEMBLIX vs bosutinib1,2

8% of patients taking SCEMBLIX discontinued treatment, compared to 26% of patients taking bosutinib due to adverse reactions

8% of patients taking SCEMBLIX discontinued treatment, compared to 26% of patients taking bosutinib due to adverse reactions

  • 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
%

URTIa

26

0.6

12

1.3

Musculoskeletal painb

24

2.6

17

1.3

Headachec

21

1.9

16

0

Fatigued

20

0.6

11

1.3

Rashe

18

0.6

30

8

Hypertensionf

14

7

5

3.9

Abdominal paing

14

0

24

2.6

Diarrheah

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 %

Musculo​skeletal painj

42

4.2

Fatigued

31

2.1

Nausea

27

0

Rashk

27

0

Diarrhea

21

2.1

Vomiting

19

6

Headachel

19

2.1

Abdominal painm

17

8

Arthralgia

17

0

Hemorrhagen

15

2.1

Cougho

15

0

Hypertensionf

13

8

Pruritus

13

0

URTIp

13

0

Edema

10

4.2

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

SCEMBLIXq

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.