Press Release: FDA approves Novartis Kisqali(R) to reduce risk of recurrence in people with HR+/HER2- early breast cancer

Ad hoc announcement pursuant to Art. 53 LR

-- Broad indication in HR+/HER2- stage II and III early breast cancer (EBC)

at high risk of recurrence approximately doubles population eligible for

CDK4/6 inhibitor adjuvant therapy1,2

-- Kisqali(R) (ribociclib) significantly reduced the risk of recurrence by

25% vs. endocrine therapy (ET) alone; consistent benefit and a

well-tolerated safety profile seen across all subgroups in pivotal Phase

III NATALEE trial, including patients with node-negative disease3-6

-- Late-breaking NATALEE data recently presented at ESMO provides additional

confidence, with deepening of invasive disease-free survival benefit

after completion of the three-year treatment period across all patient

subgroups7

-- 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 involvement8,9

-- Already a proven treatment in HR+/HER2- metastatic breast cancer1,10-20,

Kisqali is under regulatory review worldwide, including in the EU, for

the EBC indication

Basel, September 17, 2024 -- Novartis today announced that the US Food and Drug Administration (FDA) has approved Kisqali(R) (ribociclib) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage II and III early breast cancer (EBC) at high risk of recurrence, including those with node-negative (N0) disease(1).

The approval is based on results from the pivotal Phase III NATALEE trial, which showed a significant and clinically meaningful 25.1% (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006) reduction in risk of disease recurrence in a broad population of patients with HR+/HER2- stage II and III EBC treated with adjuvant Kisqali plus endocrine therapy (ET) compared to ET alone, including those with high-risk N0 disease(3-6). The invasive disease-free survival (iDFS) benefit was consistently observed across all patient subgroups(3-6).

"The FDA approval of Kisqali for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care," said Dennis J. Slamon, M.D., Director of Clinical/Translational Research, UCLA Jonsson Comprehensive Cancer Center and Chairman of the Board of Translational Research In Oncology (TRIO) and NATALEE trial lead investigator. "Today's approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning."

In EBC, Kisqali is taken with or without food as a once-daily oral dose of 400 mg (two 200 mg tablets) for three weeks, followed by one week off treatment, in combination with four weeks of any AI(1). Patients should take Kisqali for three years. The NATALEE trial showed the safety profile of Kisqali at the 400 mg dose was well tolerated, with discontinuations mainly driven by asymptomatic laboratory findings(3). Adverse events (AEs) of special interest in the Kisqali + ET arm of the NATALEE trial include (all Grades, and Grades 3/4, respectively): neutropenia (62.5%, 44.3%), liver-related AEs (26.4%, 8.6%), QT interval prolongation (5.3%, 1.0%), and interstitial lung disease/pneumonitis (1.5%, 0.0%)(4).

An updated analysis from the NATALEE trial recently presented at the European Society for Medical Oncology (ESMO) Congress 2024 reinforces the data analyzed by the FDA. Results showed a deepening benefit beyond the three-year treatment period and reduced the risk of recurrence by 28.5% (HR=0.715; CI 95% 0.609--0.840; P<0.0001), compared to ET alone, in patients with stage II and III HR+/HER2- EBC(7). Novartis will continue evaluating NATALEE patients for longer-term outcomes, including overall survival.

Raising the bar for EBC survivors

Approximately 90% of breast cancer cases in the US are diagnosed early (stages I-III) and treated promptly with curative intent -- sometimes with adjuvant ET(2) (1) (,2) (2). In spite of this, people with stage II and III HR+/HER2- EBC remain at risk of cancer coming back -- in most cases, as incurable metastatic disease(8,9). Recurrence remains a lifelong concern, though most tumors return within the first years, even in cases with no lymph node involvement(8,23). Despite ET, 10% of people with high-risk N0 disease may face recurrence within the first three years after diagnosis(2) (4).

"With this approval, we are redefining treatment options for a broader population of people impacted by breast cancer and facing the persistent risk of recurrence," said Victor Bultó, President, US, Novartis. "We continue to transform cancer care with Kisqali, building on its established profile in the metastatic setting and now helping a wide range of people as they strive to stay cancer-free following an early-stage diagnosis."

"Breast cancer treatment can take a toll on your physical and mental health, and you may worry about the risk of your cancer coming back. This risk is different for everyone, depending on many factors, but should not be underestimated," said Valarie Worthy, Co-Founder & Vice President of Community Outreach and Engagement, Touch, The Black Breast Cancer Alliance. "The FDA approval of Kisqali for more people with breast cancer is welcome news and empowers people diagnosed with early breast cancer with a new option to help manage and control their risk of cancer coming back."

Novartis prioritizes patient access by offering the Novartis Patient Support program. This resource assists eligible patients in navigating treatment initiation, providing educational materials, clarifying insurance coverage, and identifying potential financial assistance options. For additional information, patients and healthcare professionals can call 1-800-282-7630.

About NATALEE

NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali(R) (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(25). The adjuvant ET in both treatment arms was a non-steroidal AI (NSAI; anastrozole or letrozole) and goserelin if applicable(25). The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria(25). A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial(25).

About Kisqali(R) (ribociclib)

Kisqali(R) (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.

Beyond today's FDA approval of Kisqali for EBC patients in the US, 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 US FDA and the European Commission(1,2) (6). In the US, 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 men(1). 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 agonist(2) (6).

In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials(10-20). The NCCN Guidelines(R) 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- MBC(2) (7). 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 cancer(2) (8). 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 line(2) (9).

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 35 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.

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September 17, 2024 12:55 ET (16:55 GMT)