Novartis Kisqali® adds one more year of survival benefit for broadest set of patients, including those with aggressive HR+/HER2- advanced breast cancer

• New large pooled exploratory analysis from MONALEESA-2, -3 and -7 reinforces unparalleled overall survival (OS) benefit of Kisqali plus ET compared to ET alone, in HR+/HER2- aBC patients with challenging visceral metastases¹
  
  
• Kisqali plus endocrine therapy reports a median OS of approximately five years in patients with visceral metastases, adding a nearly one-year survival benefit compared to ET alone in this harder-to-treat population¹
  
  
• Kisqali is a unique CDK4/6 inhibitor, consistently demonstrating statistically significant OS benefit while maintaining or improving quality of life across three Phase III trials, regardless of patient or disease characteristics^1-12

Basel, September 9, 2022 — Novartis today announced results from a new pooled exploratory analysis across the entire MONALEESA Phase III program, confirming nearly one year of additional overall survival (OS) benefit in a subgroup of patients with aggressive forms of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer (aBC)¹. This subgroup analysis found that patients with visceral metastases—including liver metastases and multiple metastatic sites, which are typically associated with a poor prognosis—who were treated with Kisqali^® (ribociclib) plus endocrine therapy in the first-line setting, achieved a median OS of 62.7 months compared to 52.1 months for those treated with endocrine therapy alone (HR=0.79; 95% CI: 0.65-0.97)¹. Data from this analysis will be presented at the European Society of Medical Oncology (ESMO) Congress in Paris, France.

“Patients who have visceral metastases typically have a worse prognosis and often demonstrate resistance to treatment, so as a clinician it is encouraging to see significant survival benefit with ribociclib in the first-line setting in patients with more aggressive disease,” said Denise A. Yardley, MD, Senior Investigator, Breast Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, USA. “Ribociclib is the only CDK4/6 inhibitor to show a consistent overall survival benefit in combination with endocrine therapy, while also maintaining quality of life across the Phase III program.”

Those with liver metastases on Kisqali plus endocrine therapy in the first-line achieved 44.2 months median OS compared to 38.1 months for those on endocrine therapy alone (HR=0.77; 95% CI: 0.55-1.07). For patients with visceral metastases in three or more organs, first-line
treatment with Kisqali-endocrine therapy achieved 57.7 months median OS compared to 49.3 months for those on endocrine therapy alone (HR=0.81; 95% CI: 0.63-1.03)¹.

“The goal for advanced breast cancer treatment is to help people live longer, and we are proud that Kisqali continues to deliver a significant survival benefit while also maintaining quality of life, even for those with harder-to-treat disease,” said Jeff Legos, Executive Vice President, Global Head of Oncology and Hematology at Novartis. “We are committed to demonstrating what makes Kisqali a unique CDK4/6 inhibitor, thus providing patients and oncologists confidence in this therapeutic option.”

HARMONIA head-to-head CDK4/6 inhibitor trial design
Also at ESMO, the trial design will be presented for HARMONIA, the first prospective, head-to-head Phase III trial of CDK4/6 inhibitors being conducted in collaboration with SOLTI Innovative Cancer Research, to evaluate Kisqali vs. Ibrance^®* (palbociclib) for patients with advanced HR+/HER2-, HER2-enriched subtype, ultimately exploring what makes Kisqali unique at a molecular level¹³. HARMONIA seeks to test if Kisqali improves the course of HR+/HER2- aBC by changing tumor biology to enable a better response to endocrine therapy as compared to Ibrance*, and could further substantiate differences seen among these CDK4/6 inhibitors. HER2-enriched is an intrinsic subtype associated with a very poor prognosis and endocrine-resistance, as compared to luminal disease. The global, multicenter, randomized, open-label, Phase III study has a primary outcome of progression-free survival (PFS), and secondary outcomes include OS and PFS2. HARMONIA is currently ongoing with an anticipated enrollment of 456 patients.

About Kisqali^® (ribociclib)
Kisqali is the only CDK4/6 inhibitor with proven overall survival benefit across all its three pivotal Phase III advanced breast cancer trials^2-12, and is recognized by the National Comprehensive Cancer Network (NCCN) guidelines as the only CDK4/6 inhibitor with overall survival benefit in first-line HR+/HER2- advanced breast cancer¹⁴. Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line premenopausal patients with HR+/HER2- advanced breast cancer¹⁵. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6i, received a score of four out of five for postmenopausal patients with HR+/HER2- advanced breast cancer treated in the first line¹⁶.

Kisqali has been approved in more than 95 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission, for the treatment of women with HR+/HER2- advanced or metastatic breast cancer in combination either with an aromatase inhibitor or with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy^13,17. Kisqali in combination with fulvestrant is approved as initial endocrine-based therapy or following disease progression on endocrine therapy in men by the FDA¹⁷.

Novartis is committed to continuing to study Kisqali in breast cancer. NATALEE is a large Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)¹⁸. Additionally, Novartis is collaborating with the Akershus University Hospital in Norway on the NEOLETRIB trial, a neoadjuvant Phase II trial studying the effects of Kisqali in HR+/HER2- early breast cancer and to discover the potentially unique underlying mechanism of action¹⁹.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We've taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with metastatic breast cancer.

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
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References

1. Yardley DA, Yap YS, et al. Pooled exploratory analysis of survival in patients (pts) with HR+/HER2- advanced breast cancer (ABC) and visceral metastases (mets) treated with ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) trials. Presented at the Europeian Society of Medical Oncology (ESMO) Congress. September 9-13, 2022. Abstract #205P.
2. Neven P, Fasching PA, et al. Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Presented at the European Society for Medical Oncology (ESMO) Breast Cancer Congress. May 4, 2022. Abstract #LBA4, May 4, 2022.
3. Hortobagyi, et al. Overall Survival With Ribociclib Plus Letrozole in Advanced Breast Cancer. N Engl J Med 2022; 386:942-50. 
4. Hortobagyi, et al. Overall survival (OS) results from the phase III MONALEESA (ML)-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at the European Society of Medical Oncology (ESMO) Congress, September 16-21, 2021. Abstract #LBA17. 
5. Im, S. A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019; 381:307-316. 
6. Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im S-A, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020;382(6):514–24. 
7. Slamon, DJ, et al. Overall survival (OS) results of the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor 2–negative (HER2−) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Presented at the European Society of Medical Oncology (ESMO) Congress, September 29, 2019, Barcelona, Spain. Abstract #LBA7. 
8. Slamon D, Neven P, Chia S, et al. Updated overall survival (OS) results from the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 5, 2021. Abstract #1001. 
9. Tripathy D, Im S-A, Colleoni M, et al, Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at the San Antonio Breast Cancer Symposium, December 9, 2020. Abstract #PD2-04. 
10. Yardley, Denise, A. et. al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #1054. 
11. O’Shaughnessy J et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium, December 7-10, 2021. Abstract #GS2-01. 
12. Novartis Data on File. Novartis Pharmaceuticals Corp: 2021.
13. Pascual T, Stover D, et al. HARMONIA SOLTI-2101/AFT-58: A head-to-head phase III study comparing ribociclib (RIB) and Palbociclib (PAL) in patients with hormone receptor-positive/HER2-negative/HER-Enriched (HR+/HER2-/HER2-E) advanced breast cancer (ABC). Presented at the European Society of Medical Oncology (ESMO) Congress. September 9-13, 2022. Abstract #272TiP.
14. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Breast Cancer. Version 1.2022.
15. European Society for Medical Oncology – Magnitude of Clinical Benefit Scale Scorecard. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-158-1. Published April 20, 2020. Updated August 21, 2020. Accessed September 9, 2020.
16. European Society for Medical Oncology – Magnitude of Clinical Benefit Scale Scorecard. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-9-1. Published March 29, 2022. Accessed April 1, 2022.
17. Kisqali (ribociclib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation.
18. Novartis Pharmaceuticals and Translational Research in Oncology (2018, December 7 – 2026, May 29). A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer (NATALEE). Identifier NCT03701334. https://clinicaltrials.gov/ct2/show/NCT03701334.
19. Novartis and Vestre Viken Hospital Trust (2022, April 1 – 2024, December 1). Neoadjuvant Treatment of Locally-advanced Breast Cancer Patients With Ribociclib and Letrozole (NEOLETRIB). Identifier NCT05163106. https://clinicaltrials.gov/ct2/show/NCT05163106.
    
    

*Ibrance^® is a registered trademark of Pfizer Inc.

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