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

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 24 weeks

Key secondary END POINT²

MMR at 96 weeks

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^® (asciminib) tablets 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 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

At the early time point of Week 24, SCEMBLIX improved efficacy across response end points vs bosutinib in the ≥3rd-line setting.¹

The MMR rate at 48 weeks was 29% (95% CI, 22-37) in patients receiving SCEMBLIX and 13% (95% CI, 6.5-23) in patients receiving bosutinib. With a median duration of follow-up of 20 months (range: 1 day to 36 months), the median duration of response had not yet been reached for patients with MMR at any time.¹

Patients achieved MR4 and MR4.5 at 24 weeks²

MR4 or deeper: 10.8% of patients on SCEMBLIX vs 5.3% on bosutinib
MR4.5: 8.9% of patients on SCEMBLIX vs 1.3% on bosutinib

A DIFFERENCE IN CUMULATIVE MMR RATES ACROSS TIME POINTS WAS DEMONSTRATED²

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

Median follow-up was 14.9 months²

The median duration of treatment was 67 weeks (range: 0.1 to 162 weeks) for patients receiving SCEMBLIX and 30 weeks (range: 1 to 149 weeks) for patients receiving bosutinib.¹

Efficacy in Adults with Ph+ CML-CP Who Have the T315I Mutation

DEMONSTRATED EFFECTIVENESS IN 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 study

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

MMR by Week 24 was achieved by 58% (n=11/19) in ponatinib-naive patients vs 31% (n=8/26) for patients pretreated with ponatinib¹¹
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}

_{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 is defined as 0% to 35% Ph+ metaphases.¹²
MR4 is defined as BCR-ABL1^IS ≤0.01%.²
MR4.5 is defined as BCR-ABL1^IS ≤0.0032%.²}

_{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.}

_{^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.}

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

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

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

_{^gNonresponders were censored at their last molecular assessment date.}

_{^hDiscontinuation from treatment for any reason, without prior achievement of MMR, is considered a competing event.}

_{References: 1. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 2. Rea D, Mauro M, Boquimpani C, et al. Blood. 2021;[in press]. 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 DW, 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. ABL001 Investigator’s Brochure. Novartis Pharmaceuticals Corp; 2021. 12. Data on file. CABL001A2301 clinical study report. Novartis Pharmaceuticals Corp; 2021.}

Learn more about the SCEMBLIX safety profile >

*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.

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