Longer-term data for Novartis Scemblix® reinforce superior efficacy with favorable safety and tolerability profile in adults with newly diagnosed CML

• Scemblix demonstrated sustained superior major molecular response (MMR) vs. all investigator-selected TKIs (74.1% vs. 52%) and vs. imatinib alone (76.2% vs. 47.1%), meeting both ASC4FIRST 96-week key secondary endpoints¹  
• Scemblix showed a clinically relevant 15.1% higher MMR rate vs. second generation (2G) TKIs (72.0% vs. 56.9%)¹ 
• 96-week data extend favorable safety and tolerability profile for Scemblix vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs and less than half the discontinuation rate due to AEs¹ 
• Latest results strengthen Scemblix as a standard of care following expanded indication in newly diagnosed and previously treated adult patents with Ph+ CML-CP and NCCN category 1 recommendation^1-3 

East Hanover, December 8, 2024 – Novartis today announced positive, longer-term results from the pivotal Phase III ASC4FIRST trial with Scemblix^® (asciminib) showing superior major molecular response (MMR) rates at week 96¹. The study compared the MMR rate of Scemblix to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib and bosutinib) and to imatinib alone in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) at the week 96 evaluation, the study’s key secondary endpoints¹. The longer-term results showed an increasing difference in Scemblix MMR rate vs. SoC, vs. imatinib and vs. 2G TKIs (nilotinib, dasatinib and bosutinib)¹. Results were presented at the 66^th American Society of Hematology Annual Meeting & Exposition (ASH)¹.

“These 96-week results are very encouraging for clinicians who aspire to obtain a balance of efficacy and tolerability profiles to help newly diagnosed adult CML patients achieve and maintain treatment goals,” said Jorge Cortes, M.D., Director, Georgia Cancer Center. “The sustained superior efficacy, deeper and more durable responses, and favorable safety and tolerability profile compared to standard of care TKIs continue to support the promise of Scemblix as a potentially practice-changing treatment option.” 

The median follow-up was 2.2 years for Scemblix and investigator-selected SoC TKIs¹. Over 22% more patients treated with once-daily Scemblix achieved MMR at week 96 vs. all investigator-selected SoC TKIs, and nearly 30% more patients achieved MMR at week 96 vs. imatinib alone¹. The Scemblix MMR rate was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher vs. 2G TKIs (72% vs. 56.9%)¹. Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs¹. 

The safety profile of Scemblix at 96-weeks was consistent with the 4-year follow-up of the Phase III ASCEMBL trial, with no new safety concerns observed to date^1,2,4. Fewer grade ≥3 AEs and dose adjustments to manage AEs were reported for Scemblix, and discontinuation due to AEs was more than 50% lower for Scemblix vs. both imatinib and 2G TKIs¹. The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash¹. 

Novartis also presented today at ASH interim data from the Phase II ASC2ESCALATE dose-escalation study in both the second line (2L) and newly diagnosed Ph+ CML-CP settings⁵. In the analysis of 2L patients at week 24 (n=28) Scemblix demonstrated MMR rates of 42.9% and deep molecular responses (MR4 25% and MR4.5 10.7%), with a consistent safety and tolerability profile⁵. The most common AEs (>15%) were nausea, hypertension, and vomiting⁵. 

“Novartis’ decades-long work in CML and deep relationships within the community have informed our Scemblix clinical trial program of over 10 years, the centerpiece of our continuing drive to address ongoing unmet medical needs for people with CML,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “These latest findings reinforce the differentiated efficacy, safety and tolerability profile of Scemblix in newly diagnosed and previously treated adult CML patients.” 

Scemblix was recently granted accelerated approval in the US to treat newly diagnosed adults with Ph+ CML-CP, which together with its approval in previously treated adult patients with Ph+ CML-CP expands the population of Scemblix-eligible patients by four-fold ². In addition, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for the treatment of CML, recommending asciminib as a category 1 – preferred treatment for newly diagnosed Ph+ CML-CP and across all risk categories³. 

About the ASC4FIRST Phase III Clinical Trial 
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix^® 80 mg QD vs. IS first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP^2,6. The trial met both primary endpoints with Scemblix demonstrating superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%) as well as the secondary, non-powered endpoint for the 2G TKI stratum of (66% vs 57.8%)^1,6. The study remains ongoing with further efficacy and safety readouts planned.  

About the ASC2ESCALATE Phase II Study 
ASC2ESCALATE (NCT05384587) is a Phase II, multicenter, single-arm, dose-escalation study of oral Scemblix^® 80 mg QD in both the second line (2L) and newly diagnosed (1L) Ph+ CML-CP settings in the US ^5,7. While Scemblix is already approved across lines of therapy, this is the first prospective trial to assess asciminib in the 2L setting and a dose-escalation strategy of asciminib as 2L and 1L treatment for patients with CML-CP not meeting molecular milestones ⁵. The proportion of patients achieving MMR at 12 months in the 2L setting will be measured as the primary endpoint ⁵. The study remains ongoing and has completed enrollment with 196 patients (100 patients in 2L, 96 patients in 1L)⁵.  

About Scemblix^® (asciminib) 
Scemblix^® is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)^4,8,9. Other currently approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive)⁹.  

In the US, Scemblix was granted accelerated approval to treat newly diagnosed adults with Ph+ CML-CP and is also approved for previously treated adult patients with Ph+ CML-CP. Outside the US, it is approved in more than 75 countries, including the EU, to treat those who have previously been treated with two or more TKIs with Ph+ CML-CP^2,10,11. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation^2,3,10. 

Scemblix is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination^{2,4,6,8,10,12-24}. 

Patient Access and Support  
Novartis, with its 20+ year history in CML, is committed to continuing to address areas of unmet patient need and reducing barriers to patient access and affordability that prevent patients from benefiting from innovation. Novartis Patient Support is available to help guide eligible patients through the various aspects of getting started on treatment including help understanding insurance coverage and identifying potential financial assistance options. Patients or providers can call 866-433-8000 or visit support.scemblix.com to learn more. 

About Novartis Commitment to CML 
Novartis has a long-standing scientific commitment to patients living with CML. For more than two decades, our bold science has helped transform CML from a life-limiting condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation – we continue to lead the way in developing novel medicines to address serious unmet needs in CML. Our commitment also goes beyond science. Our 20+ year collaboration with the Max Foundation has provided access to Gleevec (imatinib), Tasigna (nilotinib) and now Scemblix and is delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date. 

Indications
SCEMBLIX^® (asciminib) tablets is a prescription medicine used to treat adults with newly diagnosed or previously treated Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP). The approval of SCEMBLIX in patients newly diagnosed is based on a study that measured major molecular response (MMR) rate. There are ongoing studies to confirm the clinical benefit of SCEMBLIX for this use and how SCEMBLIX works over a longer period of time. SCEMBLIX is also approved for use in adults with Ph+ CML in CP with the T315I mutation. It is not known if SCEMBLIX is safe and effective in children.

Important Safety Information
SCEMBLIX^® (asciminib) tablets may cause low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and low red blood cell counts (anemia). Patients should tell their doctor right away if they have unexpected bleeding or easy bruising; blood in their urine or stools; fever; or any signs of an infection. SCEMBLIX may increase enzymes in the patient’s blood called amylase and lipase, which may be a sign of inflammation of the pancreas (pancreatitis). Patients should tell their doctor right away if they have severe stomach-area (abdominal) pain or discomfort, nausea, or vomiting. During treatment with SCEMBLIX, doctors may check the patient’s blood pressure and treat any high blood pressure as needed. Patients should tell their doctor if they develop high blood pressure or symptoms of high blood pressure including confusion, headaches, dizziness, chest pain, or shortness of breath.

If a patient has an allergic reaction while on SCEMBLIX, they should stop taking SCEMBLIX and get medical help right away. Signs or symptoms of an allergic reaction include trouble breathing or swallowing; feeling dizzy or faint; swelling of the face, lips, or tongue; fever; skin rash or flushing of their skin; or a fast heartbeat. SCEMBLIX may cause heart and blood vessel problems, including heart attack; stroke; blood clots or blockage of a patient’s arteries; heart failure; and abnormal heartbeat, which can be serious and may sometimes lead to death. In the majority of cases, these heart and blood vessel problems can happen in people with risk factors or a history of these problems and previously treated with other tyrosine kinase inhibitor (TKI) medicines. Patients should tell their doctor right away if they get shortness of breath; chest pain or pressure; a feeling like their heart is beating too fast or they feel abnormal heartbeats; swelling in their ankles or feet; dizziness; weight gain; numbness or weakness on one side of their body; decreased vision or loss of vision; trouble talking; pain in their arms, legs, back, neck, or jaw; headache; or severe stomach-area (abdominal) pain.

Before taking SCEMBLIX, patients should tell their doctor about all of their medical conditions, including if they have a history of pancreatitis; a history of heart problems or blood clots in their arteries and veins (types of blood vessels). SCEMBLIX can harm an unborn baby. Women should tell their doctor right away if they become pregnant or think they may be pregnant during treatment with SCEMBLIX. Women who are able to become pregnant should have a pregnancy test before they start SCEMBLIX and should use effective birth control (contraception) during treatment and for 1 week after the last dose of SCEMBLIX. Women should not breastfeed during treatment and for 1 week after their last dose of SCEMBLIX. SCEMBLIX may cause fertility problems in females. This may affect their ability to have a child.

Patients should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. Taking SCEMBLIX with certain other medicines may affect each other causing side effects and may affect the way that SCEMBLIX works. The most common side effects of SCEMBLIX include muscle, bone, or joint pain; rash; tiredness; nose, throat, or sinus (upper respiratory tract) infections; headache; stomach-area (abdominal) pain; and diarrhea. The most common blood test abnormalities include decreased blood counts of white blood cells, platelets, red blood cells and blood calcium corrected levels; and increased blood levels of pancreas enzymes (amylase and lipase), blood fat (triglycerides and cholesterol), uric acid, liver enzymes, alkaline phosphatase, or creatine kinase.

Please see full Prescribing Information for SCEMBLIX, available at https://www.novartis.us/sites/www.novartis.us/files/scemblix.pdf.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and https://www.novartis.us and connect with us on LinkedIn, LinkedIn US, Facebook, X/Twitter, X/Twitter US and Instagram.

References  

1. Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic Myeloid Leukemia in ASC4FIRST: Week 96 Update. Presented at: 66th ASH Annual Meeting & Exposition; December 7 – 10, 2024; San Diego, CA.      
2. Scemblix (asciminib) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; October 2024.  
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Chronic Myeloid Leukemia Version 2.2025. November 13, 2024. Accessed November 22, 2024. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf      
4. Rea D, Mauro MJ, Boquimpani C, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After 2 or more prior TKIs. Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984  
5. Atallah EL, Levy MY, Koller P, et al. Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI). Presented at: 66th ASH Annual Meeting & Exposition; December 7 – 10, 2024; San Diego, CA.      
6. A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP (ASC4FIRST). ClinicalTrials.gov identifier: NCT04971226. Updated March 25, 2024. Accessed March 26, 2024. https://clinicaltrials.gov/study/NCT04971226     
7. Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (ASC2ESCALATE) ClinicalTrials.gov identifier: NCT05384587. Updated October 30, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT05384587  
8. Cortes JE, Hughes TP, Mauro MJ, et al. Asciminib, a First-in-Class STAMP Inhibitor, Provides Durable Molecular Response in Patients (pts) with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: Primary Efficacy and Safety Results from a Phase 1 Trial. Oral presentation at: ASH Annual Meeting; Dec. 7, 2020.   
9. Schoepfer J, Jahnke W, Berellini G, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018;61(18):8120-8135. doi:10.1021/acs.jmedchem.8b01040  
10. Novartis data on file.   
11. Scemblix. EMA Summary of Product Characteristics. Novartis Europharm Limited; 2022.  
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13. Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326. doi:10.1056/NEJMoa1902328      
14. Hughes TP, et al. Expanded Phase 1 Study of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and Durable Responses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy. Presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.    
15. Ottmann OG, Alimena G, DeAngelo DJ, et al. ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy. Blood. 2015;126(23):138. doi:10.1182/blood.V126.23.138.138    
16. Mauro MJ, Kim DW, Cortes J, et al. Combination of Asciminib Plus Nilotinib (NIL) or Dasatinib (DAS) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019.    
17. Cortes JE, Lang F, Kim DW, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019.    
18. Manley PW, Barys L, Cowan-Jacob SW. The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase. Leuk Res. 2020;98:106458. doi:10.1016/j.leukres.2020.106458    
19. Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. ClinicalTrials.gov identifier: NCT03106779. Updated February 7, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03106779    
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23. A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL. ClinicalTrials.gov identifier: NCT02081378. Updated March 18, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT02081378    
24. Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. ClinicalTrials.gov identifier: NCT04948333. Updated February 28, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04948333