- 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® (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 sub-groups 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
EAST
HANOVER, N.J., Sept. 17,
2024 /PRNewswire/ -- Novartis today announced that
the US Food and Drug Administration (FDA) has approved
Kisqali® (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)
disease1.
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 disease3-6. The invasive disease-free
survival (iDFS) benefit was consistently observed across all
patient subgroups3-6.
"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
AI1. 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 findings3. 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- EBC7. 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
ET21,22. 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 disease8,9. Recurrence remains a
lifelong concern, though most tumors return within the first years,
even in cases with no lymph node involvement8,23.
Despite ET, 10% of people with high-risk N0 disease may face
recurrence within the first three years after
diagnosis24.
"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 Kisqali
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® (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 TRIO25. The adjuvant ET in both treatment arms was
a non-steroidal AI (NSAI; anastrozole or letrozole) and goserelin
if applicable25. The primary endpoint of NATALEE is iDFS
as defined by the Standardized Definitions for Efficacy End Points
(STEEP) criteria25. A total of 5,101 adult patients with
HR+/HER2- EBC across 20 countries were randomized in the
trial25.
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.
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 Commission1,26. 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 men1.
In MBC, Kisqali has consistently demonstrated statistically
significant overall survival benefit across three Phase III
trials10-20. 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.
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," "to reduce," "remains,"
"continue," "transform," "evaluate," "likelihood," "ensuring,"
"updates," "should," or similar terms, or by express or implied
discussions regarding potential marketing approvals, new
indications or labeling for Kisqali in combination with an
aromatase inhibitor (AI), or regarding potential future revenues
from such product. 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 Kisqali in combination
with an AI 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 Kisqali in
combination with an AI will be commercially successful in the
future. In particular, our expectations regarding Kisqali in
combination with an AI 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.
Reimagine medicine with us: Visit us at
https://www.novartis.com and
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