Novartis Scemblix®, with novel mechanism of action, shows superior, long-term efficacy and consistent tolerability in 96-week follow-up of chronic myeloid leukemia trial

• Scemblix^® (asciminib) continues to show superior efficacy with more-than-two-fold improvement in major molecular response rate vs. Bosulif^®* (bosutinib) at 96 weeks (37.6% vs. 15.8%), building on 24-week results^1,2

• Long-term safety remains consistent, with discontinuation rates due to adverse events more than three times lower in the Scemblix vs. Bosulif arm (7.7% vs. 26.3%)^1,2

• Updated results continue to support the use of Scemblix in patients with Philadelphia chromosome-positive CML in chronic phase previously treated with two or more TKIs, and its potential to transform the standard of care with a differentiated mechanism of action^1,2

• Clinical development program continues, evaluating Scemblix across multiple lines of treatment in CML, with additional data being presented at the European Hematology Association 2022 Hybrid Congress

Basel, June 7, 2022 — Novartis today announced longer-term follow-up data from the Phase III ASCEMBL trial for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors (TKIs), presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. In this analysis, the proportion of patients in the Scemblix^® (asciminib) arm (n=157) who achieved a major molecular response (MMR) at 96 weeks was more than double that in the Bosulif^® (bosutinib) arm (n=76) (37.6% vs. 15.8% [P=.001]), substantially increasing from previous analyses^1,2. Additionally, the probability of maintaining MMR for at least 72 weeks for patients treated with Scemblix was 96.7% (95% CI, 87.4%–99.2%), reflecting long-term durability of efficacy¹.

Despite longer duration of exposure for patients in the Scemblix arm – with a median of 23.7 months vs. 7.0 months for patients in the Bosulif arm – the updated 96-week analysis showed the proportion of patients treated with Scemblix who discontinued treatment due to adverse events (AEs) continued to be more than three times lower than those treated with Bosulif (7.7% vs. 26.3%). No new on-treatment deaths were reported since the primary analysis at 24 weeks^1,2.

“In a chronic cancer where resistance can develop to many of the existing therapies, or where patients can have their quality of life negatively impacted by treatment side effects over time, it’s encouraging to see sustained and increasing efficacy with consistent adequate tolerability for patients treated with Scemblix in the longer term,” said Jorge E. Cortes, MD, Director, Georgia Cancer Center, Augusta University. “This 96-week data shows the potential of Scemblix and its unique mechanism of action to help change the treatment paradigm in CML.”

Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket³. With this novel mechanism of action, it is also known in scientific literature as STAMP inhibitor, Scemblix can help address resistance to TKI therapy in patients with Ph+ CML-CP and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells^2,4-10. Scemblix continues to be studied across multiple lines of treatment for CML-CP^11-18.

In addition to durable responses consistent with the primary analysis, more patients treated with Scemblix than Bosulif had BCR::ABL1≤1% (45.1% vs 19.4%) at 96 weeks. The most frequent (>10% in any treatment arm) grade ≥3 AEs on Scemblix vs. Bosulif, respectively, were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%)¹. The values for these AEs were similar to the values reported at the 24 and 48 week analyses^1,2,19.

“These longer-term results offer a more robust view of the promising potential of Scemblix, and will help support ongoing regulatory filings as we seek to bring this therapy to more patients across the globe,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis. “As leaders in CML treatment innovation, we believe that with Scemblix, we have the potential to once again transform the standard of care for people affected by this disease.”

Visit https://www.hcp.novartis.com/virtual-congress/a-2022/ for the latest information from Novartis at ASCO, including our bold approach to reimagining cancer care, and access to our ASCO data presentations. Additional updates on trials evaluating Scemblix in earlier lines of therapy – as well as for patients with the T315I mutation – will be presented at the upcoming European Hematology Association 2022 Hybrid Congress, with more information available at https://www.hcp.novartis.com/virtual-congress/eha-2022/.

About Scemblix^® (asciminib)
Scemblix (asciminib) is FDA-approved for the treatment of adult patients with Ph+ CML-CP pre-treated with two or more TKIs, as well as adult patients with Ph+ CML-CP with the T315I mutation. The first indication is approved under the US FDA Accelerated Approval Program based on MMR rate at 24 weeks; continued approval for the first indication may be contingent upon verification and description of clinical benefit from confirmatory evidence³.

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 monotherapy and in combination^2,11-18. 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 plan¹².

Regulatory reviews for Scemblix in multiple countries and regions across the globe are ongoing. These updated 96-week ASCEMBL results are being shared with regulatory authorities, as we seek to bring Scemblix to more patients in more countries across the globe.

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. Cortes JE, et al. Oral presentation at ASCO 2022; June 3-7, 2022. Chicago, IL and virtual. Abstract 7004.
2. 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. 2022. DOI: 10.1182/blood.2020009984. PMID: 34407542.
3. Scemblix [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
4. Wylie AA, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1. Nature. 2017;543(7647):733-737. 4.
5. 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.
6. Hughes TP, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. ClinicalTrials.gov. 2021 Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. [online] Available at: https://clinicaltrials.gov/ct2/show/NCT04948333
18. 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
19. Mauro, JM. Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, Vs Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase after ≥2 Prior Tyrosine Kinase Inhibitors: Update after 48 Weeks. Oral presentation at: ASH Annual Meeting; Dec. 11, 2021. Abstract #310.

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