Press Release: Novartis Scemblix(R) Phase III data first to show superior efficacy with a favorable safety and tolerability profile vs. standard-of-care TKIs in adults with newly diagnosed CML

===
-- Phase III ASC4FIRST trial met both primary endpoints with clinically
meaningful and statistically significant results; Scemblix(R) (asciminib)
demonstrated 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%)1

-- Scemblix also demonstrated a favorable safety and tolerability profile
vs. imatinib and 2G TKIs, with fewer grade >=3 AEs, dose adjustments, and
half the rate of AEs leading to treatment discontinuation1
-- TKIs have transformed CML treatment, but unmet need remains; many newly
diagnosed patients do not meet molecular response goals, and many
discontinue or change treatment due to intolerance2-17

-- Scemblix was granted US FDA Breakthrough Therapy Designation, submission
is now in review under the agency's Oncology Center of Excellence RTOR
program; data will be presented as a plenary at EHA and today as a
late-breaking abstract at ASCO
===
Basel, May 31, 2024 -- Novartis today presents positive results from the pivotal Phase III ASC4FIRST trial as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) meeting. Scemblix(R) (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, dasatinib and bosutinib, and compared to imatinib alone in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP)(1) . Scemblix also showed a numerical improvement in MMR at week 48 vs. second generation (2G) TKIs (nilotinib, dasatinib and bosutinib)(1) . Additionally, Scemblix demonstrated a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations vs. both imatinib and 2G TKIs(1) .

"Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs," said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). "When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals."

The median follow-up was 16.3 and 15.7 months for Scemblix and investigator-selected SoC TKIs, respectively(1) . Nearly 20% more patients treated with Scemblix achieved MMR at week 48 vs. investigator-selected SoC TKIs and nearly 30% more patients achieved MMR at week 48 vs. imatinib alone(1) . Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs and imatinib alone(1) .

===

Overall(a)           Imatinib stratum(b)     2G TKI stratum(c) 
Scemblix (n=201)          Scemblix (n=101)     Scemblix (n=100) vs. 
vs. investigator-selected   vs. imatinib (n=102)     2G TKIs (n=102) 

SoC TKIs (n=204)

-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MMR          67.7% vs. 49.0%           69.3% vs. 40.2%               -- 
Primary endpoints          rates 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MMR               18.9%                     29.6% 
Treatment             (9.6%--28.2%)            (16.9%--42.2%)               -- 

difference (95%
CI)
----------------------- ---------------- -------------------------- --------------------- ---------------------
Adjusted 1-sided <.001 <.001 -- p-value

-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MMR                 --                       --               66.0% vs. 57.8% 
Secondary endpoints(d)       rates 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MR4            39% vs. 21%               43% vs. 15%            35% vs. 26% 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 
Week 48 MR4.5            17% vs. 9%               18% vs. 5%             16% vs. 13% 
-----------------------  ----------------  --------------------------  ---------------------  --------------------- 

(a) All patients receiving Scemblix (n=201) or investigator-selected
SoC TKIs (n=204). Treatment difference after adjusting
for pre-randomization selected TKI and EUTOS long-term
survival (ELTS) risk groups at baseline.
(b) The 203 patients within the pre-randomization-selected
imatinib stratum were randomized to receive either
Scemblix (n=101) or imatinib (n=102). Treatment difference
after adjusting for ELTS risk groups at baseline.
(c) The 202 patients within the pre-randomization
selected 2G TKIs stratum were randomized to receive
either Scemblix (n=100) or 2G TKIs (n=102: nilotinib,
48%; dasatinib, 41%; bosutinib, 11%).
(d) Secondary endpoints were not powered for statistical
significance.

===
In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed(1) . Fewer grade >=3 AEs, dose adjustments to manage AEs, and half the rate of AEs leading to treatment discontinuation were reported for Scemblix vs. both imatinib and 2G TKIs(1) .

===

Scemblix  Imatinib  2G TKIs 
-------------------------------------------------  --------  --------  ------- 
Grade >=3 AEs(a)                        38%       44%      55% 
-------------------------------------------------  --------  --------  ------- 
AEs leading to treatment discontinuation(a)           5%       11%      10% 
-------------------------------------------------  --------  --------  ------- 
AEs leading to dose adjustments/ interruptions(a)       30%       39%      53% 
-------------------------------------------------  --------  --------  ------- 

(a) In patients who experienced >=1 adverse event.

===
"Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. "The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation."

CML is a chronic condition and the side effects of standard-of-care can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching," said Gerald Clements, CML caregiver, patient advocate and Steering Committee Treasurer at CML Advocates Network. "Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start."

The trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints(18) .

These results have been submitted to the US Food and Drug Administration (FDA) via the Oncology Center of Excellence Real-Time Oncology Review (RTOR) program and Scemblix has been granted Breakthrough Therapy Designation. They will also be presented as a plenary at the European Hematology Association (EHA) 2024 Congress in June.

About ASC4FIRST Phase III Clinical Trial

ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix(R) 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP(18) . The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 48(18) .

The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 96(18) . The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) and BCR::ABL1 <=1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival and overall survival(18) .

About Scemblix(R) (asciminib)

Scemblix(R) is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)(19-21) . The current approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive) (21) .

(MORE TO FOLLOW) Dow Jones Newswires

May 31, 2024 08:00 ET (12:00 GMT)

Press Release: Novartis Scemblix(R) Phase III -2-

Scemblix is approved in more than 70 countries, including the US and the EU, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs(22-2) (4) . In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation(23-25) .

Scemblix is an important treatment option for patients who experience resistance and/or intolerance after two prior TKI therapies(2-17) , and it is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination(18-2) (0) (,24) (,26-3) (8) .

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 into a chronic, vs. 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 collaboration with the Max Foundation has provided access to Glivec, Tasigna and now Scemblix, starting over 20 years ago, and delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date.

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/ https://www.novartis.com and connect with us on https://www.linkedin.com/company/novartis/ LinkedIn, https://www.facebook.com/novartis/ Facebook, https://twitter.com/Novartis X/Twitter and https://instagram.com/novartis?igshid=MzRlODBiNWFlZA==__;!!N3hqHg43uw!pjp8z253J5NjaOYrW65UbAAlHeHRdQ-w0m4ezZxEQEl0ptafXN2M99VRIk39pf49PAc8NbK93Pxp3uaSBQkAf8oEnzWXG8Sk$ Instagram.

References

===
1. Hughes TP, Hochhaus A, Takahashi N, et al. ASC4FIRST, a pivotal ph 3
study of asciminib (ASC) vs investigator-selected tyrosine kinase
inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic
myeloid leukemia (CML): primary results [abstract]. Presented at:
American Society for Clinical Oncology (ASCO) 2024 Annual Meeting; May 31
-- June 4, 2024; Chicago, IL.

2. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of
frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic
phase: 5-year update of the randomized ENESTnd trial. Leukemia.
2016;30(5):1044-1054. doi:10.1038/leu.2016.5

3. Brümmendorf TH, Cortes JE, de Souza CA, et al. Bosutinib versus
imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia:
results from the 24-month follow-up of the BELA trial. Br J Haematol.
2015;168(1):69-81. doi:10.1111/bjh.13108

4. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib Versus
Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the
Randomized BFORE Trial. J Clin Oncol. 2018;36(3):231-237.
doi:10.1200/JCO.2017.74.7162

5. Kota VK, Wei D, Yang D, et al. Treatment Patterns and Modifications of
Tyrosine Kinase Inhibitors (TKI) Therapy in Early Lines in Patients with
Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Real-World Analysis
from a Large Commercial Claims Database in the United States (US). Blood.
2023;142:5190.

6. Hehlmann R, Cortes JE, Zyczynski T, et al. Tyrosine kinase inhibitor
interruptions, discontinuations and switching in patients with
chronic-phase chronic myeloid leukemia in routine clinical practice:
SIMPLICITY. Am J Hematol. 2019;94(1):46-54. doi:10.1002/ajh.25306

7. Claudiani S, Chughtai F, Khan A. et al. Long-term outcomes after upfront
second-generation tyrosine kinase inhibitors for chronic myeloid
leukemia: managing intolerance and resistance. Leukemia.
2024;38:796--802. doi:10.1038/s41375-024-02187-w

8. Kohlbrenner K, Galuschek N, Fabarius A, et al. Therapy in Patients with
Chronic Myeloid Leukemia Outside of Clinical Trials: Results of the
German CML-Registry (CML-VI). Blood. 2022;140(Supplement 1):947--949.
doi:10.1182/blood-2022-159412

9. Cortes JE, Khoury HJ, Kantarjian HM, et al. Long-term bosutinib for
chronic phase chronic myeloid leukemia after failure of imatinib plus
dasatinib and/or nilotinib. Am J Hematol. 2016;91(12):1206-1214.
doi:10.1002/ajh.24536

10. Garg RJ, Kantarjian H, O'Brien S, et al. The use of nilotinib or
dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term
follow-up. Blood. 2009;114(20):4361-4368.
doi:10.1182/blood-2009-05-221531

11. Steegmann JL., Baccarani M, Breccia M, et al. European LeukemiaNet
recommendations for the management and avoidance of adverse events of
treatment in chronic myeloid leukaemia. Leuk. 2016;30:1648-1671.
doi:10.1038/leu.2016.104

12. Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib
Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017;376: 917--927.
doi:10.1056/NEJMoa1609324

13. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of
DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve
Chronic Myeloid Leukemia Patients Trial. J Clin Oncol. 2016;34:2333-2340.
doi:10.1200/JCO.2015.64.8899

14. Akard LP, Albitar M, Hill CE, Pinilla-Ibarz, J. The "Hit Hard and Hit
Early" Approach to the Treatment of Chronic Myeloid Leukemia:
Implications of the Updated National Comprehensive Cancer Network
Clinical Practice Guidelines for Routine Practice. Clin Adv Hematol
Oncol. 2013;11(7):421-432.

15. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety
in Philadelphia chromosome--positive leukemia: final 5-year results of
the phase 2 PACE trial. Blood. 2018;132(4):393-404.
doi:10.1182/blood-2016-09-739086

16. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020
recommendations for treating chronic myeloid leukemia. Leuk.
2020;34:966-984. doi:10.1038/s41375-020-0776-2

17. Flis S, Chojnacki T. Chronic myelogenous leukemia, a still unsolved
problem: pitfalls and new therapeutic possibilities. Drug Des Devel Ther.
2019;13:825-843. doi:10.2147/DDDT.S191303

18. 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

19. 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.
===
(MORE TO FOLLOW) Dow Jones Newswires

May 31, 2024 08:00 ET (12:00 GMT)

===
doi:10.1182/blood.2020009984

20. 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.

21. 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

22. Scemblix. EMA Summary of Product Characteristics. Novartis Europharm
Limited; 2022.

23. Scemblix. US FDA Prescribing Information. Novartis Pharmaceuticals; 2021.

24. Novartis data on file.

25. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines
in Oncology (NCCN Guidelines(R)) Chronic Myeloid Leukemia Version 2.2024.
December 5, 2023. Accessed April 3, 2024.
https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf

26. Wylie AA, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001
enables dual targeting of BCR--ABL1. Nature. 2017;543(7647):733-737.
doi:10.1038/nature21702

27. 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

28. 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.

29. 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

30. 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.

31. 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.

32. 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

33. 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

34. Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase
(CML-CP) With and WithoutT315I Mutation (AIM4CML). ClinicalTrials.gov
identifier: NCT04666259. Updated September 7, 2023. Accessed April 3,
2024. https://clinicaltrials.gov/ct2/show/NCT04666259

35. Study of Efficacy And Safety Of Asciminib In Combination With Imatinib In
Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP).
ClinicalTrials.gov identifier: NCT03578367. Updated March 22, 2024.
Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03578367

36. Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib
Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine
Kinase Inhibitors. ClinicalTrials.gov identifier: NCT04795427. Updated
October 19, 2023. Accessed April 3, 2024.
https://clinicaltrials.gov/ct2/show/NCT04795427

37. 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

38. 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
===
# # #

===

Novartis Media Relations
E-mail: media.relations@novartis.com

Central                                                North America 
Anja von Treskow                     +41 79 392 9697       Michael Meo  +1 862 274 5414 
Anna Schäfers                   +41 79 801 7267  Marlena Abdinoor  +1 617 335 9525 

Switzerland
Satoshi Sugimoto +41 79 619 2035

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com

Central                                                  North America 
Isabella Zinck                       +41 61 324 7188     Sloan Simpson  +1 862 345 4440 
Nicole Zinsli-Somm                   +41 61 324 3809   Jonathan Graham  +1 201 602 9921 
Imke Kappes                          +41 61 324 8269     Parag Mahanti  +1 973 876 4912 

===
(END) Dow Jones Newswires

May 31, 2024 08:00 ET (12:00 GMT)