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2016-12-09

Novartis International AG: Novartis LEE011 (ribociclib) plus letrozole analyses show superior PFS across broad spectrum of patients in first-line HR+/HER2- adva

Novartis International AG / Novartis LEE011 (ribociclib) plus letrozole
analyses show superior PFS acrossbroad spectrum of patients in first-line
HR+/HER2- advanced breast cancer versus letrozole. Processed and transmitted
by Nasdaq Corporate Solutions. The issuer is solely responsible for the
content of this announcement.
* MONALEESA-2 analyses demonstrate superior PFS with LEE011 plus letrozole in
pre-defined patient subgroups - from de novoto bone, liver and lung
metastases - compared to letrozole alone
* LEE011 plus letrozole reduced risk of progression or death by 55% over
letrozole alone in de novopatients, and by 54% in patients with three or
more metastases - the most aggressive form of the disease
* Consistent with overall study population, m ost adverse events were mild to
moderate, identified early through routine monitoring, and generally
managed through dose interruption and reduction
* FDA granted LEE011 Breakthrough Therapy designation and Priority Review,
which may lead to faster access for US patients

Basel, December 9, 2016
-
Novartis announced today additional analyses from the Phase III MONALEESA-2
study that show LEE011 (ribociclib) plus letrozole significantly prolonged
progression-free survival (PFS) across pre-planned patient subgroups with
hormone receptor positive, human epidermal growth factor receptor-2 negative
(HR+/HER2-) advanced or metastatic breast cancer, including post-menopausal
women diagnosedde novo
, those with visceral liver and lung metastases, and those with bone-only
disease[1],[2].

These findings demonstrate the strength of LEE011 plus letrozole in the
first-line setting, showing that treatment benefit was evident across all
patient subgroups regardless of their disease burden or tumor location,
including those patients with aggressive disease. Data will be presented
today at the San Antonio Breast Cancer Symposium (SABCS) (Abstracts P4-22-05
and P4-22-16).

"Results from thede novo
subgroup of women in the MONALEESA-2 trial establish ribociclib in combination
with letrozole as a meaningful treatment option in the first-line setting for
this patient population," said Joyce O'Shaughnessy, MD, Co-Chair, Breast
Cancer Research, Texas Oncology-Baylor Charles A. Sammons Cancer Center.
"Thesede novo
patients are often diagnosed initially with advanced breast cancer that has
already metastasized, so it is critical to start them with treatments that
extend time until disease progression."

"Breast cancer that has metastasized to areas such as the liver or lungs can
often be more challenging to effectively treat with current standards of
care," said Howard A. Burris, MD, President, Clinical Operations and Chief
Medical Officer, Sarah Cannon. "We have been encouraged by the MONALEESA-2
results because treatment benefit was observed regardless of the number of
metastatic sites and was maintained across all subgroups taking ribociclib
plus letrozole. Our observations indicate that this novel therapy may be a
promising treatment option for many patients living with advanced forms of
breast cancer."

First-line ribociclib + letrozole in patients withde novo
HR+, HER2- advanced breast cancer: A subgroup analysis of the MONALEESA-2
trial (Abstract P4-22-05)

A predefined subgroup analysis of the MONALEESA-2 trial evaluated the safety
and efficacy of LEE011 plus letrozole versus letrozole alone in 227 patients
withde novo
advanced breast cancer, defined as disease found to be metastatic at the time
of first diagnosis[1]. Becausede novo
disease has not been previously treated with systemic treatment for
early-stage breast cancer, tumors may exhibit a different disease biology,
which could result in varied responses compared to patients who experienced
recurrence[1]. In patients withde novo
advanced breast cancer, LEE011 plus letrozole reduced the risk of disease
progression or death by 55% over letrozole alone (HR=0.448 [95% CI:
0.267-0.750])[1]. The 12-month PFS rate was 82% in the LEE011 plus letrozole
arm compared to 66% with letrozole alone.

Consistent with the overall study population, most adverse events were mild to
moderate in severity, identified early through routine monitoring, and
generally managed through dose interruption and reduction[1]. The most common
grade 3/4 adverse events (>=15% of patients withde novo
advanced breast cancer; LEE011 plus letrozole vs. letrozole alone) were
neutropenia (55.3% vs. 0.9%) and leukopenia (21.1% vs. 0%)[1].

First-line ribociclib + letrozole in patients with HR+, HER2- advanced breast
cancer presenting with visceral metastases or bone-only disease: A subgroup
analysis of the MONALEESA-2 trial (Abstract P4-22-16)

In separate predefined subgroups, 393 patients with advanced breast cancer
with visceral metastases and 147 patients with bone-only disease were
evaluated as part of the MONALEESA-2 trial. Those with visceral metastases
have metastatic growth at the site of the lung or liver, and typically have a
poorer prognosis than patients with non-visceral disease[2]. Results of these
analyses show that first-line LEE011 plus letrozole was well tolerated and
reduced the risk of disease progression or death by 47% (patients with
visceral disease: HR=0.535 [95% CI: 0.385-0.742]) and by 31% (patients with
bone-only disease: HR=0.690 [95% CI: 0.381-1.249]) respectively[2]. Treatment
benefit with LEE011 in combination with letrozole was observed regardless of
the number of metastatic sites and (HR=0.607 (95% CI: 0.437-0.845) among
patients with less than 3 metastases; HR=0.456 (95% CI: 0.298-0.700) among
patients with 3 or more metastases)[2].

Among patients with visceral metastases the most frequent grade 3/4 adverse
events (>=20% of patients; LEE011 plus letrozole vs. letrozole alone) were
neutropenia (64.0% vs 1%) and leukopenia (20.8% vs 0.5%)[2]. Among patients
with bone-only disease the most frequent grade 3/4 adverse events (>=20% of
patients; LEE011 plus letrozole vs. letrozole alone) were neutropenia (53.6%
vs 1.3%) and leukopenia (23.2% vs 1.3%)[2].

"These additional results from the MONALEESA-2 study are very promising for
women with HR+ advanced breast cancer," said Bruno Strigini, CEO, Novartis
Oncology. "We believe LEE011 could significantly benefit a broad range of
women as an initial treatment for metastatic breast cancer and look forward
to working with global health authorities to bring this new treatment to
patients."

The MONALEESA-2 study is ongoing to evaluate secondary endpoints, including
overall survival. LEE011 received Breakthrough Therapy designation from the
US Food and Drug Administration (FDA) in August 2016 and Priority Review in
October 2016.

About LEE011 (ribociclib)

LEE011 (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 in a cell, can enable cancer cells to grow and divide too
quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring
cancer cells do not grow uncontrollably.

LEE011 is not approved for any indication in any market at this time. LEE011
was developed by the Novartis Institutes for BioMedical Research (NIBR) under
a research collaboration with Astex Pharmaceuticals.

About the MONALEESA Clinical Trial Program

Novartis is continuing to assess LEE011 through the robust MONALEESA
(MammaryONcologyAssessment ofLEE011'sEfficacy andSAfety) clinical trial
program, which includes MONALEESA-2, MONALEESA-3, and MONALEESA-7. These
trials are evaluating LEE011 in multiple endocrine therapy combinations
across a broad range of patients, including men and premenopausal women.

MONALEESA-2 is a Phase III randomized, double blind, placebo controlled,
multicenter global registration trial to evaluate the safety and efficacy of
LEE011 in combination with letrozole compared to letrozole alone in
postmenopausal women with HR+/HER2- advanced breast cancer who received no
prior therapy for their advanced breast cancer[3].

The trial randomized 668 patients in a 1:1 ratio stratified by the presence of
liver and/or lung metastases at 223 clinical trial sites globally[3].
Patients received LEE011 600 mg/daily (three weeks on and one week off), or
placebo, in combination with letrozole 2.5 mg/daily.

The primary endpoint of the trial was PFS[3]. Secondary endpoints included:
overall survival, overall response rate, clinical benefit rate,
health-related quality of life, safety and tolerability[3].

In MONALEESA-2, the most common grade 3/4 (most severe) adverse events were as
follows for LEE011 plus letrozole compared to letrozole alone: neutropenia
(60% vs 1%), leukopenia (21% vs 1%), elevated alanine aminotransferase (9% vs
1%), lymphopenia (7% vs 1%) and elevated aspartate aminotransferase (6% vs
1%)[1]. The most common all-grade adverse events (>=35% of patients in either
arm, regardless of relationship to study treatment) were as follows for
LEE011 plus letrozole compared to letrozole alone: neutropenia (74% vs 5%),
nausea (52% vs 29%), infections (50% vs 42%), fatigue (37% vs 30%), and
diarrhea (35% vs 22%)[1]. Nausea, infections, fatigue, and diarrhea were
mostly grade 1 or 2[1].

The MONALEESA-3 trial is a phase III trial evaluating LEE011 in combination
with fulvestrant compared to fulvestrant alone in men and post-menopausal
women with HR+/HER2- advanced breast cancer who have received no or a maximum
of one prior endocrine therapy.

MONALEESA-7, the largest phase III trial of a CDK4/6 inhibitor in this patient
population, is investigating LEE011 in combination with endocrine therapy and
goserelin compared to endocrine therapy and goserelin alone in pre-menopausal
women with HR+/HER2- advanced breast cancer who have not previously received
endocrine therapy. Both MONALEESA-3 and MONALEESA-7 are fully enrolled.

About Advanced Breast Cancer

Up to one-third of patients with early-stage breast cancer will subsequently
develop metastatic disease[4]. Metastatic breast cancer is the most serious
form of the disease and occurs when the cancer has spread to other parts of
the body, such as the brain, bones or liver[5]. Advanced breast cancer
comprises metastatic breast cancer (stage 4) and locally advanced breast
cancer (stage 3)[5]. Survival rates for women living with advanced breast
cancer are lower than those for women with earlier stage disease. The 5-year
relative survival rate for stage 3 breast cancer is approximately 72%, while
metastatic (stage 4) breast cancer has a 5-year relative survival rate of
approximately 22%[6].

About Novartis in advanced breast cancer

For more than 25 years, Novartis has been at the forefront of driving
scientific advancements for breast cancer patients and improving clinical

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