Novartis receives positive CHMP opinion for Scemblix®, a novel treatment for adult patients with chronic myeloid leukemia

• With unique STAMP mechanism of action, Scemblix could provide a new option for patients in Europe with chronic myeloid leukemia (CML) who have suffered intolerance or inadequate response with at least two prior tyrosine kinase inhibitor treatments¹

• Positive opinion based on data from pivotal Phase III ASCEMBL trial, showing a near doubling in major molecular response rate for patients treated with Scemblix^® (asciminib) vs. Bosulif^®* (bosutinib) (25.5% vs. 13.2%) and more than three times lower discontinuation rate due to adverse reactions (5.8% vs 21.1%) at 24 weeks¹

• CHMP recommendation comes after the approval of Scemblix by the US FDA and other countries’ regulatory authorities, potentially broadening access for more patients to Novartis transformative therapies in CML

Basel, June 24, 2022 — Novartis today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion and recommended granting marketing authorization for Scemblix^® (asciminib) for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). If approved, Scemblix will be the first CML treatment in Europe that works by specifically targeting the ABL myristoyl pocket (also known as a STAMP inhibitor in scientific literature), representing an important therapeutic advancement for patients who experience intolerance and/or resistance to currently available TKI therapies¹.

It is estimated that, every year, more than 6,300 people will be diagnosed with CML in Europe². While many patients will benefit from available TKI therapies, a significant proportion may experience intolerance or resistance to these treatments^3-10. In an analysis of patients with CML treated with two prior TKIs, approximately 55% reported intolerance to previous treatment; and a pooled analysis of patients in the second-line setting revealed that up to 70% are unable to achieve major molecular response (MMR) within two years of follow-up^11-14.

"Although CML treatments have advanced over the last 20 years, many patients continue to experience side effects and resistance to treatment, affecting their quality of life and putting them at risk of disease progression or even death," says Dr. Andreas Hochhaus, Head of the Department of Hematology and Medical Oncology at Jena University Hospital in Germany. "If approved, the novel mechanism of action of Scemblix brings us another option to combat these challenges faced by patients — offering new hope in the management of their disease."

The positive CHMP opinion for Scemblix is based on results from the pivotal Phase III ASCEMBL trial, which showed a near doubling of MMR rate for patients treated with Scemblix vs. Bosulif®* (bosutinib) (25.5% vs. 13.2%) at 24-weeks, with a more than three times lower discontinuation rate due to adverse reactions (5.8% vs. 21.1%)¹. The most common (incidence ≥ 20%) adverse reactions reported in this analysis were thrombocytopenia (29.5%) and neutropenia (23.1%) in the Scemblix arm; and diarrhea (71.1%), nausea (46.1%), increased ALT (28.9%), vomiting (26.3%), rash (23.7%), increased AST (21.1%) and neutropenia (21.1%) in the Bosulif arm¹.

These results were confirmed in longer-term follow-up, where the MMR rate at week 96 was more than double with Scemblix (37.6%, 95% CI: 29.99-45.65) compared with Bosulif (15.8%, 95% CI: 8.43-25.96). This data was shared at oral presentations during the American Society for Clinical Oncology (ASCO) and the European Hematology Association (EHA) annual meetings in June 2022^15,16.

“We are pleased with the recommendation of Scemblix and hope to offer patients living with CML in Europe timely access to this innovative therapy, if approved,” said Haseeb Ahmad, President, Europe, Novartis. “We’ve worked relentlessly to improve CML care over the past two decades, and must seize this opportunity to help patients in need achieve better outcomes. With the strong clinical results seen to-date, we believe we have the potential to transform the standard of care in CML yet again with Scemblix.”

The CHMP recommended approval of Scemblix in CML will be referred to the European Commission (EC). The EC will review the CHMP recommendations and deliver a final decision in the coming months.

About Scemblix^® (asciminib)
Scemblix is the first CML treatment that acts as a STAMP inhibitor, specifically targeting the ABL myristoyl pocket¹. This novel mechanism of action may help address resistance in patients with CML previously treated with two or more TKIs and overcome mutations at the defective BCR::ABL1 gene, which is associated with the over-production of leukemic cells^1,17-23.

Scemblix represents an important development for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for CML-CP, both as a monotherapy and in combination^1,17-31. Specifically, the ASC4FIRST Phase III study (NCT04971226) evaluates Scemblix in newly diagnosed adult patients with Ph+ CML-CP vs. an investigator-selected TKI, with recruitment proceeding ahead of plan²⁵.

Novartis has initiated regulatory filings for Scemblix in multiple countries and regions across the globe. In October 2021, the US FDA granted accelerated approval of Scemblix for adult patients with Ph+ CML-CP, previously treated with two or more TKIs based on MMR rate at 24 weeks, and full approval for adult patients with Ph+ CML-CP with the T315I mutation. In accordance with the Accelerated Approval Program, continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence. Further data has been shared with the FDA for evaluation ³². Scemblix has received approval in several countries outside the US for adult patients with Ph+ CML-CP with resistance or intolerance to at least two or more previous therapies.

About Novartis Commitment to CML
Novartis has a long-standing scientific commitment to patients living with CML. For more than 20 years, our bold science has helped transform CML into a chronic disease for many patients. Despite these advancements, we’re not standing still. We continue to research ways to target the disease, seeking to address the challenges with treatment resistance and/or intolerance that many patients face. Novartis also continues to reimagine CML care through its commitment to sustainable access for patients and collaboration with the global CML community.

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,” “seek,” “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 such as COVID-19; 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 reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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*Bosulif is a registered trademark of Pfizer

References

1. Rea D, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After≥ 2 Prior TKIs. Blood. 2021. DOI: 10.1182/blood.2020009984. PMID: 34407542.
2. Hoffmann, V., Baccarani, M., Hasford, J. et al. The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries. Leukemia 29, 1336–1343 (2015). https://doi.org/10.1038/leu.2015.73
3. Flis S, et al. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities. Drug Des Devel Ther. 2019;13:825-843.
4. Akard LP, et al. 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.
5. Cortes JE, 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.
6. Cortes JE, 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.
7. Garg RJ, 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
8. Hochhaus A, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966-984
9. Cortes JE., 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.
10. Steegmann JL., et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016;30:1648-1671.
11. Giles FJ, et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia. 2010; 24(7):1299–1301.
12. Kantarjian HM, et al. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood. 2010;117(4):1141-1145. doi:10.1182/blood-2010-03-277152.
13. Shah NP, et al. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica. 2010 Feb;95(2):232-40. doi: 10.3324/haematol.2009.011452. PMID: 20139391; PMCID: PMC2817025.
14. Gambacorti-Passerini C, et al. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up. Am J Hematol. 2014 Jul;89(7):732-42. doi: 10.1002/ajh.23728. Epub 2014 Apr 28. PMID: 24711212; PMCID: PMC4173127.
15. Cortes JE, et al. Oral presentation at ASCO 2022; June 3-7, 2022. Chicago IL and virtual. Abstract 7004
16. Réa D, et al. Oral presentation at EHA 2022; June 9-17, 2022. Vienna Austria and virtual. Abstract S155
17. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1. Nature. 2017;543(7647):733-737.
18. Schoepfer J, 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.
19. Hughes TP, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326.
20. 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. Poster presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.
21. Ottmann OG, 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.
22. Mauro MJ, 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. Poster presented at: EHA Annual Meeting; June 15, 2019.
23. Cortes JE, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Poster presented at: EHA Annual Meeting; June 15, 2019.
24. ClinicalTrials.gov. 2017. Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT03106779.
25. ClinicalTrials.gov. 2021. A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04971226.
26. ClinicalTrials.gov. 2020. Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and WithoutT315I Mutation (AIM4CML). [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04666259.
27. ClinicalTrials.gov. 2018. Study of Efficacy And Safety Of Asciminib In Combination With Imatinib In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP). [online] Available at: https://clinicaltrials.gov/ct2/show/NCT03578367.
28. ClinicalTrials.gov. 2021. 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. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04795427.
29. ClinicalTrials.gov. 2014. A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT02081378.
30. ClinicalTrials.gov. 2021 Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04948333
31. ClinicalTrials.gov. 2021. Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04925479 
32. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 

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