Novartis receives positive CHMP opinion for Kisqali® to help reduce risk of recurrence in people with HR+/HER2- early breast cancer

• If approved, patients in Europe with stage II or III HR+/HER2- early breast cancer (EBC) at high risk of recurrence, including those with node-negative disease, will be eligible for adjuvant treatment with Kisqali^® (ribociclib) in combination with an aromatase inhibitor¹
  
  
• Recommendation is based on the Phase III NATALEE trial, where Kisqali added to endocrine therapy (ET) significantly reduced the risk of recurrence by 25% versus ET alone across a broad population of patients with HR+/HER2- early breast cancer ²
  
  
• People with stage II or III HR+/HER2- EBC face significant risk of recurrence – often as incurable metastatic disease – despite adjuvant ET and regardless of nodal involvement^3,4
  
  
• In September, Kisqali was approved by the FDA in this setting⁵; at ESMO 2024, an updated analysis from NATALEE was presented, showing a deepening invasive disease-free survival benefit⁶

Basel, October 18, 2024 – Novartis announced today 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 Kisqali^® (ribociclib) for the adjuvant treatment of adults with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), at high risk of disease recurrence, including those with node-negative disease¹.

“One-third of people diagnosed with stage II breast cancer and more than half of those diagnosed with stage III will unfortunately experience a return of their cancer in the long term, often as metastatic disease,” said Peter A. Fasching, M.D., Professor of Translational Medicine, University Hospital Erlangen and Comprehensive Cancer Center Erlangen-EMN and NATALEE trial investigator. “If approved, Kisqali could provide an effective and tolerable adjuvant treatment option to mitigate the risk of recurrence in a broader patient population, particularly for patients who currently have limited treatment options, including those with high-risk node-negative disease.”

Breast cancer is the most commonly diagnosed cancer in Europe⁷. HR+/HER2- is the most common subtype, accounting for approximately 70% of all breast cancers, and more than 40% of these are diagnosed in stage II or III^8-10.

The positive CHMP decision is based on robust data from the Phase III NATALEE trial^2,11,12. In the trial, Kisqali plus endocrine therapy (ET), compared to ET alone, lowered the risk of cancer recurrence by 25.1% in patients with stage II and III HR+/HER2- EBC (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006) and demonstrated a consistent, clinically meaningful invasive disease-free survival (iDFS) benefit across key pre-specified subgroups^2,11. Data from the pivotal trial also showed the safety profile of Kisqali at the 400mg dose was well-tolerated with generally low-grade symptomatic adverse events^2,11.

An updated analysis from the NATALEE trial recently presented at the European Society for Medical Oncology (ESMO) Congress 2024 adds to the growing body of evidence supporting the potential of Kisqali to consistently reduce risk of recurrence across a broad population⁶. In the updated analysis, the iDFS benefit continued to deepen beyond the three-year Kisqali treatment period in all patient subgroups, including those with node-negative disease².

“Today, many people diagnosed with HR+/HER2- early breast cancer in Europe lack options beyond endocrine therapy to help reduce their risk of cancer coming back. If approved, Kisqali could nearly double the number of patients eligible for CDK4/6 inhibitor adjuvant therapy,” said Patrick Horber M.D., President, International, Novartis. “Together with the recent FDA approval and late-breaking NATALEE data presented at ESMO, today's positive CHMP recommendation further reinforces the differentiated profile of Kisqali as a new treatment option for a broad population of patients, including those with node-negative disease.”

Following the CHMP's recommendation to approve Kisqali in a broad population of patients diagnosed with HR+/HER2- EBC at high risk of recurrence, the European Commission (EC) will take a final decision within approximately two months.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali^® (ribociclib) with ET as an investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO^2,13. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable^2,13. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria^2,13. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial^2,13.

About Kisqali^® (ribociclib)
Kisqali^® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was approved as a treatment for early breast cancer by the U.S. Food and Drug Administration (FDA) in September 2024⁵. Regulatory reviews for Kisqali as an EBC treatment are ongoing worldwide, including in the EU and China.

Kisqali has been approved as a treatment for metastatic breast cancer (MBC) patients in 99 countries worldwide, including by the U.S. FDA and the European Commission^14,15. In the U.S., Kisqali is indicated for the treatment of adults 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 men¹⁴. 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 progression¹⁵. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist^14,15.

In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials^16-26. The NCCN Guidelines^® for breast cancer recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of people living with HR+/HER2- when combined with an AI, making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- MBC²⁷. 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 cancer²⁸. 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 line²⁹.

Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals.

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

About Novartis in Breast Cancer
For more than 30 years, Novartis has been at the forefront of driving scientific advancements for people touched by breast cancer and improving clinical practice in collaboration with the global community. With one of the most comprehensive breast cancer portfolios and pipeline, Novartis leads the industry in discovery of new therapies and combinations in HR+/HER2- breast cancer, the most common form of the disease.

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; 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
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.

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References

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