Basel, September 14, 2023 — Novartis today presents new patient-reported outcomes (PRO) data from the Phase III NATALEE trial at the European Society for Medical Oncology (ESMO) Virtual Plenary. The data show that a broad population of patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) maintained health-related quality of life (HRQoL) during treatment with Kisqali® (ribociclib) plus endocrine therapy (ET)¹.

“Treatment in early breast cancer is physically and emotionally arduous, and afterwards people diagnosed with EBC struggle to balance the worry of their cancer returning with the burden of managing adjuvant treatment,” said Dr. Peter A. Fasching, Professor of Gynecology and Obstetrics Translational Medicine, at the University Hospital Erlangen and Comprehensive Cancer Center Erlangen-EMN and NATALEE trial investigator. “The patient-reported outcomes from NATALEE reinforce Kisqali as a potential adjuvant option that reduces the risk of cancer returning without compromising patients’ well-being, mental health or physical abilities.”


Patients treated with Kisqali plus ET for up to three years maintained their physical functioning and global health scores when compared to both their baseline scores and to patients treated with ET alone, demonstrating that patients maintained their overall HRQoL when treated with adjuvant Kisqali¹.

“No patient should have to choose between maintaining their quality of life and doing everything they can to remain cancer free,” said Jeff Legos, Executive Vice President, Global Head of Oncology and Hematology Development at Novartis. “These patient-reported outcomes add to the wealth of efficacy and tolerability data from the NATALEE trial suggesting Kisqali is a potential adjuvant treatment of choice for a broad range of patients with HR+/HER2- EBC, including those with node-negative disease. Kisqali could enable patients with EBC to live well with greater peace of mind.”

Further analysis of the NATALEE trial is ongoing, and additional data will be shared at upcoming medical meetings.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali with ET as adjuvant treatment versus ET alone in patients with HR+/HER2- EBC, being conducted in collaboration with TRIO². The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable². The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria². A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial².

Results showed Kisqali plus ET, compared to ET alone, lowered the risk of cancer recurrence by 25.2% (HR=0.748; 95% CI: 0.618, 0.906; p=0.0014), along with consistent clinically meaningful iDFS benefit across key pre-specified subgroups: AJCC Tumor Stage II (HR=0.761; 95% CI: 0.525, 1.103), AJCC Tumor Stage III (HR=0.740; 95% CI: 0.592, 0.925), node-negative disease (HR=0.630; 95% CI: 0.341, 1.165), node-positive disease (HR=0.771; 95% CI: 0.630, 0.944), pre-menopausal women and men (HR=0.722; 95% CI: 0.530, 0.983), post-menopausal women (HR=0.781; 95% CI: 0.613, 0.997)². Kisqali data across all secondary efficacy endpoints was also consistent, including DDFS (26% risk reduction) and RFS (28% risk reduction), with a trend for improvement in OS (HR=0.759; 95% CI: 0.539, 1.068)^*2.

Median study duration of follow up was 34 months (range 21-48 months) with clinical benefits observed after approximately two years². NATALEE explored a lower starting dose (400 mg) of Kisqali than the dose approved for treatment in metastatic breast cancer (MBC) (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy. The safety profile of Kisqali at 400 mg was favorable with low rates of symptomatic AEs and limited need for dose modifications when administered up to three years². The most frequently reported AEs of special interest (grade 3 or higher) were neutropenia (43.8%) and liver-related AEs (e.g. elevated transaminases) (8.3%)².

*Results based on pre-specified interim analysis for OS at time of primary iDFS analysis; additional follow up is planned to obtain more mature OS data².

About Early Breast Cancer
More than 90% of patients diagnosed with breast cancer have EBC³. Despite standard-of-care adjuvant therapy, approximately one-third of those diagnosed with stage II and more than half of those diagnosed with stage III HR+/HER2- EBC experience cancer recurrence^4,5. The risk of recurrence continues over decades with more than half of breast cancer recurrences occurring five or more years after diagnosis^4,6. For many of these patients, there are currently no targeted therapeutic options outside of the standard chemotherapy and ET⁷.

About Kisqali® (ribociclib) 
Kisqali has consistently demonstrated OS benefit while preserving or improving quality of life across three Phase III trials in MBC^8-19. Updates to the NCCN Guidelines® for breast cancer, released in January 2023, recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an aromatase inhibitor (AI)²⁰. 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 pre-menopausal patients with HR+/HER2- advanced breast cancer²¹. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line²².

Kisqali has been approved in 99 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission. In the U.S., Kisqali is approved for the treatment of adult patients with HR+/HER2- advanced or MBC in combination with an AI as initial ET or fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men. In the EU, Kisqali is approved for the treatment of women with HR+/HER2- advanced or MBC in combination with either an AI or fulvestrant as initial ET or following disease progression. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist¹⁹.

Novartis is committed to continuing to study Kisqali in breast cancer. Novartis is collaborating with SOLTI, which is leading the HARMONIA study to test whether Kisqali changes tumor biology to enable a better response to ET compared to Ibrance®** (palbociclib) for patients with HR+/HER2-, HER2-enriched subtype²³ MBC, and with the Akershus University Hospital in Norway on the NEOLETRIB trial, a neoadjuvant Phase II trial studying the effects of Kisqali in HR+/HER2- EBC to discover the potentially unique underlying mechanism of action²⁴. 

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

Disclaimer
This media update 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 media update, 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 media update 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 media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise.

About Novartis
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References

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19. Kisqali (ribociclib) Prescribing Information.
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**Ibrance® is a registered trademark of Pfizer, Inc.

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Source:- Novartis