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

Efficacy

ASCEMBL Study Design

ASCEMBL: The first 3rd-line+ Phase 3 trial in CML evaluating efficacy and safety vs a 2nd-generation TKI comparator^1,2

Multicenter, randomized, active-controlled, and open-label study^1,2

Primary END POINT²

MMR at Week 24

Key secondary END POINT²

MMR at Week 96

Other SELECT secondary end points²

Cytogenetic response rates and MMR rates, at and by scheduled data collection time points
Time to and duration of MMR
Time to and duration of CCyR
Safety and tolerability

Key baseline characteristics

Resistance to last prior TKI: 61% of patients in the SCEMBLIX arm vs 71% with bosutinib²
Intolerance to last prior TKI: 38% of patients in the SCEMBLIX arm vs 29% with bosutinib²
MCyR at baseline: 29% of patients in the SCEMBLIX arm vs 29% with bosutinib²
Percentages of patients who had previously received 2, 3, 4, or 5 or more prior lines of TKIs were 48%, 31%, 15%, and 6%, respectively¹

Efficacy in Patients in Later Lines

For adults with Ph+ CML-CP, previously treated with ≥2 TKIs
SCEMBLIX is the first treatment to demonstrate superior response rates vs bosutinib in a Phase 3 trial^1,3-10

The MMR benefit with SCEMBLIX vs bosutinib increased over time^1,11

Median follow-up was 28 months¹

The median duration of treatment was 24 months (range: 0 to 46 months) for patients receiving SCEMBLIX and 7 months (range: 0 to 43 months) for patients receiving bosutinib.¹

SCEMBLIX more than doubled the MMR rate (38% vs 16%) at Week 96 vs bosutinib.¹

Across nearly 2 years of data, SCEMBLIX demonstrated durable response rates¹¹

Percentages of patients who had previously received 2, 3, 4, or 5 or more prior lines of TKIs were 48%, 31%, 15%, and 6%, respectively.¹

Almost all SCEMBLIX patients who achieved MMR maintained it for more than 16 months (97% probability).¹¹

SCEMBLIX demonstrated fast responses at Week 24 and increased depth of response at Week 96^1,11

More patients achieved CCyR at Week 24 with SCEMBLIX vs bosutinib¹

The CCyR rate at Week 96 was 40% (95% CI, 30-50) in patients receiving SCEMBLIX and 16% (95% CI, 8-28) for bosutinib. Note that any patients who achieved CCyR and later achieved MMR would not have been assessed for CCyR at Week 96. Of patients achieving CCyR during the study, 1 patient in the SCEMBLIX arm and 2 patients in the bosutinib arm lost response^1,11

More patients achieved MR4 and MR4.5 at Week 96 with SCEMBLIX vs bosutinib¹¹

Efficacy in Patients With the T315I Mutation

DEMONSTRATED EFFECTIVENESS IN ADULT PATIENTS WITH T315I MUTATION¹

The clinical efficacy and safety of SCEMBLIX for the treatment of patients with Ph+ CML-CP who have the T315I mutation were evaluated in a multicenter, open-label study¹

MMR was achieved by 96 weeks in 49% (95% CI, 34-64) of the patients (n=45) treated with SCEMBLIX.¹

The median duration of treatment was 108 weeks (range: 2 to 215 weeks).¹

By Week 24, MMR was achieved in 58% (n=11/19) in ponatinib-naive patients vs 31% (n=8/26) of patients pretreated with ponatinib¹²
Percentages of patients who had previously received 1, 2, 3, 4, or 5 or more TKIs were 18%, 31%, 36%, 13%, and 2.2%, respectively¹

_{Efficacy was based on 45 patients with Ph+ CML-CP who have the T315I mutation who received SCEMBLIX at a dose of 200 mg bid. Patients continued treatment until unacceptable toxicity or treatment failure occurred.¹}

_{bid, twice daily; CCyR, complete cytogenetic response; CML-CP, chronic myeloid leukemia in chronic phase; IS, International Scale; MCyR, major cytogenetic response; MMR, major molecular response; MR, molecular response; qd, once daily; TKI, tyrosine kinase inhibitor.}

_{MMR was defined as BCR::ABL1^IS ≤0.1%.¹
CCyR was defined as 0% of Philadelphia chromosome–positive metaphases in bone marrow aspirate with at least 20 examined.¹}
_{MCyR was defined as 0% to 35% Ph+ metaphases.¹¹
MR4 was defined as BCR::ABL1^IS ≤0.01%.²
MR4.5 was defined as BCR::ABL1^IS ≤0.0032%.²}

_{^aMust meet the definition of treatment failure per the 2013 European LeukemiaNet recommendations. Patients meeting treatment failure criteria on bosutinib could be switched to SCEMBLIX.}

_{^bDefined as nonhematologic grade 3 or 4 toxicity while on therapy; persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments; or hematologic grade 3 or 4 toxicity while on therapy, recurrent after dose reduction to the lowest recommended dose.}

_{^cPatients will continue to receive study treatment for up to 96 weeks after the last patient’s first dose or 48 weeks after the last patient switches to SCEMBLIX, whichever is longer.}

_{^dEstimated using a common risk difference stratified by baseline MCyR status.}

_{^eEstimated using a Cochran-Mantel-Haenszel 2-sided test stratified by baseline MCyR status.}

_{^fCCyR analysis based on patients who were not in CCyR at baseline.}

_{References: 1. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 2. Réa D, Mauro M, Boquimpani C, et al. Blood. 2021;138(21):2031-2041. 3. Kantarjian HM, Giles FJ, Bhalla KN, et al. Blood. 2011;117(4):1141-1145. 4. O’Brien SG, Guilhot F, Larson RA, et al. N Engl J Med. 2003;348(11):994-1004. 5. Saglio G, Kim D-W, Issaragrisil S, et al. N Engl J Med. 2010;362(24):2251-2259. 6. Kantarjian H, Shah NP, Hochhaus A, et al. N Engl J Med. 2010;362(24):2260-2270. 7. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. J Clin Oncol. 2018;36(3):231-237. 8. Cortes JE, Kantarjian HM, Brümmendorf TH, et al. Blood. 2011;118(17):4567-4576. 9. Shah NP, Kantarjian HM, Kim D-W, et al. J Clin Oncol. 2008;26(19):3204-3212. 10. Soverini S, Gnani A, Colarossi S, et al. Blood. 2009;114(10):2168-2171. 11. Data on file. CABL001A2301 clinical study report. Novartis Pharmaceuticals Corp; 2022. 12. Data on file. ABL001 Investigator’s Brochure. Novartis Pharmaceuticals Corp; 2021.}

Learn more about the SCEMBLIX safety profile >

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.

Efficacy

ASCEMBL Study Design

Multicenter, randomized, active-controlled, and open-label study1,2

Primary END POINT2

Key secondary END POINT2

Other SELECT secondary end points2