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2016-11-14

Novartis International AG: Novartis drug PKC412 (midostaurin) granted FDA Priority Review for newly-diagnosed FLT3-mutated AML and advanced systemic mastocytosi

Novartis International AG / Novartis drug PKC412 (midostaurin) granted FDA
Priority Review fornewly-diagnosed FLT3-mutated AML and advanced systemic
mastocytosis . Processed and transmitted by Nasdaq Corporate Solutions.The
issuer is solely responsible for the content of this announcement.
* Priority Review based on data from the largest clinical trials conducted to
date in each indication[ 1],[2]
* Designation will shorten FDA expected review time to within six months[3];
EMA also accepted the PKC412 (midostaurin) file for review
* The AML treatment strategy has remained unchanged for more than 25 years[
4] and PKC412 (midostaurin) may represent first FLT3-mutated AML drug with
a survival benefit

Basel, November 14, 2016
- Novartis today announced that the US Food and Drug Administration (FDA)
granted Priority Review to the PKC412 (midostaurin) new drug application
(NDA) for the treatment of acute myeloid leukemia (AML) in newly-diagnosed
adults with an FMS-like tyrosine kinase-3 (FLT3)
mutation, as well as for the treatment of advanced systemic mastocytosis (SM).
The premarket approval application (PMA) for the PKC412 (midostaurin)FLT3
companion diagnostic, developed in collaboration with Invivoscribe
Technologies, Inc. (IVS)* has also been accepted for review by the FDA.
Outside the US, the marketing authorization application for PKC412
(midostaurin) in these indications has already been accepted by the European
Medicines Agency (EMA).

"FLT3
-mutated AML and advanced SM are devastating and rare diseases, with
significant unmet needs due to limited existing treatment options," said
Bruno Strigini, CEO, Novartis Oncology. "This regulatory designation
signifies the importance of midostaurin as a potential therapy for these
patients who haven't had the benefit of targeted medicines."

The NDA submission for PKC412 (midostaurin) includes data from the largest
clinical trials conducted to date in each indication. In the Phase III RATIFY
trial (CALGB 10603), which investigated PKC412 (midostaurin) plus standard
chemotherapy versus placebo plus standard chemotherapy in adult patients less
than 60 years of age withFLT3
-mutated AML, those in the PKC412 (midostaurin) arm experienced a
statistically significant improvement in overall survival (OS) with a 23%
reduction in risk of death compared to the placebo arm (hazard ratio [HR] =
0.77, P = 0.0074)[1]. Based on these data, PKC412 (midostaurin) was also
granted Breakthrough Therapy designation by the FDA earlier this year for
newly-diagnosedFLT3
-mutated AML.

In the RATIFY trial, no statistically significant differences were observed in
the overall rate of grade 3 or higher hematologic and non-hematologic adverse
events (AEs) in the PKC412 (midostaurin) treatment group versus the placebo
group[5]. The most frequent all grade AEs were febrile neutropenia, nausea,
exfoliative dermatitis, vomiting, headache, petechiae (small red skin spots)
and pyrexia[5]. A total of 36 deaths occurring within 30 days of the last
dose of study drug were reported, with no difference in treatment-related
deaths observed between groups[5].

Data from the Phase II single-arm study (CPKC412D2201) evaluating the efficacy
of PKC412 (midostaurin) in patients with advanced SM were also published in
theNew England Journal of Medicine
in June 2016. The study showed that treatment with PKC412 (midostaurin)
resulted in an overall response rate of 60% (defined as complete or partial
resolution of organ damage) with a median duration of response of 24.1 months
(95% CI, 10.8-not estimated [NE]) and a median OS of 28.7 months (95% CI,
18.1-NE)[2]. The most frequent AEs were low-grade nausea, vomiting and
diarrhea. New or worsening grade 3 or 4 neutropenia, anemia and
thrombocytopenia occurred mostly in patients with pre-existing cytopenias[2].

A Priority Review designation is granted by the FDA to therapies that may
provide significant improvements in the treatment, diagnosis or prevention of
serious conditions[3]. According to the FDA, the goal is to take action on a
Priority Review application within six months, compared to 10 months under
the standard review process[3]. Novartis has been granted a growing number of
Priority Review designations by the FDA, underscoring the company's ongoing
commitment to developing innovative therapies for rare diseases or
underserved cancer patients.

Since PKC412 (midostaurin) remains investigational at this time, both within
the US and globally, Novartis opened a Global Individual Patient Program
(compassionate use program) and in the US, an Expanded Treatment Protocol, to
enable access to eligible patients with newly-diagnosed AML and advanced SM.
Physicians who wish to request PKC412 (midostaurin) for eligible patients
should contact a Novartis medical representative in their respective
countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for
more information.

About AML and theFLT3
mutation

AML is a rare and aggressive cancer of the blood and bone marrow[6]. It is the
most common acute leukemia in adults[7]. Of the approximately 350,000 people
with leukemias worldwide[8], about 25% have AML[7]. AML has a low survival
rate, with around 25% of patients surviving at 5 years[9].

AML is associated with the accumulation of blood cells that are unable to
mature properly, causing a buildup of immature "blast" cells that do not
allow room for normal blood cell development[6]. Mutations in specific genes
are found in many cases of AML, and molecular testing is recommended for
newly-diagnosed patients to help determine prognosis and best possible
treatment[4].

FLT3 is a receptor tyrosine kinase, a type of cell-surface receptor, which
plays a role in the proliferation, or increase, in the number of certain
blood cells. TheFLT3
gene mutation is one of the most common in AML, occurring in about one-third
of patients, and commonly results in faster disease progression, a higher
relapse rate and shorter survival[10]-[12].

About theFLT3
companion diagnostic

In order to help identify patients who may have aFLT3
mutation and potentially benefit from treatment with PKC412 (midostaurin),
Novartis is collaborating with IVS for the development and FDA approval of
theFLT3
companion diagnostic. The same test is being CE marked in Europe. Regulatory
submissions for the companion diagnostic are being led by IVS.

About advanced SM

Systemic mastocytosis (SM) comprises a group of rare diseases, affecting
between 1 in 20,000 to 40,000 people worldwide[13]. The disease is
characterized by uncontrolled growth and accumulation of mast cells - or
mediators of allergic responses - in one or more organs[14]. In advanced SM,
mast cells accumulate in such high quantities that they begin to cause organ
damage[15]. Patients also suffer from debilitating systemic symptoms such as
pruritus (severe itching of the skin), among other symptoms, caused by mast
cells releasing inflammatory mediators such as histamine into the blood[15].
Median OS is currently between 3.5 years to less than six months depending on
subtype[14].

The uncontrolled proliferation of mast cells is caused in many people by aKIT
gene mutation - the most common mutation, encoding the D816V substitution,
occurs in approximately 90% of patients[16]. TheKIT
gene mutation results in activation of the KIT enzyme, which triggers the
abnormal proliferation and survival of mast cells[15].

About PKC412 (midostaurin)

PKC412 (midostaurin) is an investigational, oral, multi-targeted kinase
inhibitor in development for the treatment of patients with AML with aFLT3
mutation and for patients with advanced SM. The safety and efficacy profile
has not been fully established, and it is not approved for any indication in
any market at this time. There is no guarantee that PKC412 (midostaurin) will
become commercially available.

Disclaimer

The foregoing release contains forward-looking statements that can be
identified by words such as "Priority Review," "will," "expected," "may,"
"potential," "Breakthrough Therapy designation," "goal," "growing,"
"commitment," "investigational," "potentially," "currently," "in
development," "at this time," or similar terms, or by express or implied
discussions regarding potential marketing approvals for PKC412, or regarding
potential future revenues from PKC412. You should not place undue reliance on
these statements. Such forward-looking statements are based on the current
beliefs and expectations of management 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
PKC412 will be submitted or approved for sale in any market, or at any
particular time. Nor can there be any guarantee that PKC412 will be
commercially successful in the future. In particular, management's
expectations regarding PKC412 could be affected by, among other things, the
uncertainties inherent in research and development, including unexpected
clinical trial results and additional analysis of existing clinical data;
unexpected regulatory actions or delays or government regulation generally;
the company's ability to obtain or maintain proprietary intellectual property
protection; general economic and industry conditions; global trends toward
health care cost containment, including ongoing pricing pressures; unexpected
safety, quality or manufacturing issues, 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 provides innovative healthcare solutions that address the evolving
needs of patients and societies. Headquartered in Basel, Switzerland,
Novartis offers a diversified portfolio to best meet these needs: innovative
medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the
only global company with leading positions in these areas. In 2015, the Group
achieved net sales of USD 49.4 billion, while R&D throughout the Group
amounted to approximately USD 8.9 billion (USD 8.7 billion excluding
impairment and amortization charges). Novartis Group companies employ
approximately 118,000 full-time-equivalent associates. Novartis products are
available in approximately 180 countries around the world. For more
information, please visithttp://www.novartis.com.

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