Novartis ribociclib (Kisqali®) recognized as Category 1 preferred breast cancer adjuvant treatment by NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Ribociclib (Kisqali) plus aromatase inhibitor (AI) recommended for HR+/HER2- early breast cancer (EBC) node-positive and high-risk node-negative patients, as studied in the NATALEE trial and indicated by the FDA1
Recommendation comes after recent FDA approval and positive CHMP Opinion for ribociclib (Kisqali) to help reduce the risk of recurrence in EBC
Ribociclib (Kisqali) is also the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- metastatic breast cancer in combination with an AI1

EAST HANOVER, N.J., Oct. 24, 2024 /PRNewswire/ — This month, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for breast cancer were updated to recommend ribociclib (Kisqali®) as a Category 1 preferred CDK4/6 inhibitor (CDK4/6i) adjuvant therapy for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) in combination with an aromatase inhibitor (AI)1. Ribociclib (Kisqali) is the only CDK4/6i recommended for both all node-positive disease as well as for patients with no nodal involvement with high-risk disease characteristics, such as tumor size >5 cm, or for tumors sized 2-5 cm, either Grade 2 with high genomic risk/Ki-67 ≥20% or Grade 31.

“These evidence-based guidelines are helpful to clinicians when determining optimal treatment options for patients,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “Importantly, the NCCN Guideline recommendation of ribociclib in this broad population reaffirms the importance of offering eligible patients with early breast cancer, including those with limited nodal involvement and high-risk N0 disease, a CDK4/6i treatment like ribociclib in addition to endocrine therapy to reduce their risk of recurrence.”

A Category 1 recommendation by the NCCN Guidelines indicates high levels of clinical evidence and uniform consensus among NCCN on ribociclib (Kisqali) as an appropriate treatment for these patients. This recommendation comes after the presentation of longer-term results from the Phase III NATALEE trial at the European Society for Medical Oncology (ESMO) Congress 2024, which showed a deepening efficacy benefit beyond the Kisqali treatment duration in a broad population of patients, including those with node-negative disease; as well as the recent FDA approval and CHMP positive opinion for Kisqali in the EBC indication2.

The updated guidelines, consistent with the FDA indication per the NATALEE trial, approximately double the number of patients that could benefit from treatment with a CDK4/6i in the adjuvant setting3.

NCCN Guidelines also continue to recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6i for first-line treatment of patients with HR+/HER2- metastatic breast cancer in combination with an AI; ribociclib (Kisqali) is also recommended as a Category 1 preferred regimen for first- and subsequent-line therapies** in HR+/HER2- MBC in combination with fulvestrant1.

To access NCCN Guidelines, visit www.nccn.org.

* Adjuvant treatment with Kisqali has only been studied in high-risk patients.
** If CDK4/6 inhibitor was not previously used.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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.

In addition to the recent FDA approval of Kisqali for EBC patients in the US and CHMP positive opinion in Europe, regulatory reviews for Kisqali as an EBC treatment are ongoing worldwide.

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 Commission4,5. 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 men4.

In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials6-16.

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.

Indication

What is KISQALI?

KISQALI® (ribociclib) is a prescription medicine used to treat adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer:

in combination with an aromatase inhibitor for stage II and III early breast cancer with a high risk of coming back
that has gotten worse or has spread to other parts of the body (advanced or metastatic breast cancer) in combination with:

an aromatase inhibitor as the first endocrine-based therapy; or
fulvestrant as the first endocrine-based therapy or following disease progression on endocrine therapy

It is not known if KISQALI is safe and effective in children.

IMPORTANT SAFETY INFORMATION

KISQALI may cause serious side effects, including:

Lung problems. KISQALI may cause severe or life-threatening inflammation of the lungs during treatment that may lead to death. Tell your health care provider right away if you have any new or worsening symptoms, including:

trouble breathing or shortness of breath
cough with or without mucus
chest pain

Severe skin reactions. Tell your health care provider or get medical help right away if you get severe rash or rash that keeps getting worse; reddened skin; flu-like symptoms; skin pain or burning, blistering of the lips, eyes, or mouth, blisters on the skin or skin peeling, with or without fever.

Heart rhythm problems (QT prolongation). KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death.

Your health care provider should check your heart and do blood tests before and during treatment with KISQALI
Tell your health care provider right away if you have a change in your heartbeat (a fast or irregular heartbeat), or if you feel dizzy or faint

Liver problems. KISQALI can cause serious liver problems. Your health care provider should do blood tests to check your liver before and during treatment with KISQALI. Tell your health care provider right away if you get any of the following signs and symptoms of liver problems:

yellowing of your skin or the whites of your eyes (jaundice)
dark or brown (tea-colored) urine
feeling very tired
loss of appetite
pain on the upper right side of your stomach area (abdomen)
bleeding or bruising more easily than normal

Low white blood cell counts (neutropenia). Low white blood cell counts are very common during treatment with KISQALI and may result in infections that may be severe. Your health care provider should check your white blood cell counts before and during treatment with KISQALI. Tell your health care provider right away if you have signs and symptoms of low white blood cell counts or infections, such as fever and chills.

Your health care provider may tell you to decrease your dose, temporarily stop, or completely stop taking KISQALI if you develop certain serious side effects during treatment with KISQALI.

What should I tell my health care provider before taking KISQALI?

Before you take KISQALI, tell your health care provider if you:

have any heart problems, including heart failure, irregular heartbeats, and QT prolongation
have ever had a heart attack
have a slow heartbeat (bradycardia)
have high blood pressure that is not controlled
have decreased thyroid gland (hypothyroidism)
have problems with the amount of potassium, calcium, phosphorus, or magnesium in your blood
have fever, chills, or any other signs or symptoms of infection
have liver problems
have kidney problems
are pregnant, or plan to become pregnant. KISQALI can harm your unborn baby

If you are able to become pregnant, your health care provider should do a pregnancy test before you start treatment with KISQALI
Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI
Talk to your health care provider about birth control methods that may be right for you during this time
If you become pregnant or think you are pregnant, tell your health care provider right away

are breastfeeding or plan to breastfeed. It is not known if KISQALI passes into your breast milk. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. KISQALI and other medicines may affect each other, causing side effects. Know the medicines you take. Keep a list of them to show your health care provider or pharmacist when you get a new medicine.

What should I avoid while taking KISQALI?

Avoid eating grapefruit and avoid drinking grapefruit juice during treatment with KISQALI since these may increase the amount of KISQALI in your blood.

The most common side effects of KISQALI in people with early breast cancer include:

decreased white blood cell counts
decreased red blood cell counts
increased liver function tests
infections
increased kidney function test
decreased platelet counts
nausea
headache
tiredness

The most common side effects of KISQALI in people with advanced or metastatic breast cancer include:

decreased white blood cell counts
decreased red blood cell counts
increased liver function tests
infections
nausea
increased kidney function test
tiredness
decreased platelet counts
diarrhea
vomiting
headache
constipation
hair loss
cough
rash
back pain
low blood sugar level

KISQALI may cause fertility problems in males, which may affect your ability to father a child. Talk to your health care provider if this is a concern for you.

Tell your health care provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of KISQALI. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see accompanying full Prescribing Information including Patient Information.

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,” “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; 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 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

NCCN Guidelines. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Breast Cancer. Accessed October 2024. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
Fasching PA. Adjuvant Ribociclib (RIB) Plus Nonsteroidal Aromatase Inhibitor (NSAI) in Patients (Pts) With HR+/HER2− Early Breast Cancer (EBC): 4-Year Outcomes From the NATALEE Trial. LBA13. Proffered Paper presented at the European Society for Medical Oncology Congress; September 16, 2024; Barcelona, Spain.
Tarantino P, Rugo HS, Curigliano G, et al. Characteristics of real-world NATALEE and monarchE eligible populations: A US electronic health records database analysis. Poster presented at the European Society for Medical Oncology Congress; September 13-17, 2024; Barcelona, Spain.
Kisqali (ribociclib) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; October 2024.
Kisqali. Summary of product characteristics (SmPC). Novartis Europharm Limited; 2017. Accessed September 2024. https://www.ema.europa.eu/en/documents/product-information/kisqali-epar-product-information_en.pdf.
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. Poster presented at the European Society of Medical Oncology Congress; September 9-13, 2022; Paris, France.
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). Mini oral presented at the European Society for Medical Oncology Breast Cancer Congress; May 4, 2022; Paris, France.
Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663
Hortobagyi GN, 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. Proffered paper presented at the European Society of Medical Oncology Congress; September 16-21, 2021; Lugano, Switzerland.
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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; San Antonio, USA.
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