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Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice

ID: 1519290
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(Thomson Reuters ONE) -
Novartis International AG /
Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM)
(CTL019), for children and young adults with B-cell ALL that is refractory or
has relapsed at least twice
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The issuer is solely responsible for the content of this announcement.

* First-in-class therapy showed an 83% (52/63) overall remission rate in this
patient population with limited treatment options and historically poor
outcomes [1],[2].
* Novel approach to cancer treatment is the result of pioneering CAR-T cell
therapy collaboration with University of Pennsylvania
* Reproducible, flexible and validated manufacturing process builds on years
of global clinical trial experience at our facility in New Jersey, US
* Novartis also announces innovative collaboration with the US Centers for
Medicare and Medicaid Services

Basel, August 30, 2017 - Novartis announced today that the US Food and Drug
Administration (FDA) has approved Kymriah((TM))(tisagenlecleucel) suspension for
intravenous infusion, formerly CTL019, the first chimeric antigen receptor T
cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with
B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in
second or later relapse. Kymriah is a novel immunocellular therapy and a one-
time treatment that uses a patient''s own T cells to fight cancer. Kymriah is the
first therapy based on gene transfer approved by the FDA.

"At Novartis, we have a long history of being at the forefront of transformative
cancer treatment," said Joseph Jimenez, CEO of Novartis. "Five years ago, we
began collaborating with the University of Pennsylvania and invested in further
developing and bringing what we believed would be a paradigm-changing
immunocellular therapy to cancer patients in dire need. With the approval of

Kymriah, we are once again delivering on our commitment to change the course of
cancer care."

"We are so proud to be part of this historic moment in cancer treatment and are
deeply grateful to our researchers, collaborators, and the patients and families
who participated in the Kymriah clinical program," said Bruno Strigini, CEO of
Novartis Oncology. "As a breakthrough immunocellular therapy for children and
young adults who desperately need new options, Kymriah truly embodies our
mission to discover new ways to improve patient outcomes and the way cancer is

The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for
Kymriah. The REMS program serves to inform and educate healthcare professionals
about the risks that may be associated with Kymriah treatment. To support safe
patient access, Novartis is establishing a network of certified treatment
centers throughout the country which will be fully trained on the use of Kymriah
and appropriate patient care.

There has been an urgent need for novel treatment options that improve outcomes
for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose
prognosis is poor. Patients often undergo multiple treatments including
chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than
10% of patients survive five years [2], [3].

Kymriah is an innovative immunocellular therapy that is a one-time treatment.
Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to
enhance cellular expansion and persistence. In 2012, Novartis and the University
of Pennsylvania (Penn) entered into a global collaboration to further research,
develop and commercialize CAR-T cell therapies, including Kymriah, for the
investigational treatment of cancers.

"This therapy is a significant step forward in individualized cancer treatment
that may have a tremendous impact on patients'' lives," said Carl June, MD, the
Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular
Immunotherapies in Penn''s Perelman School of Medicine, who is a pioneer of this
new treatment. "Through our collaboration with Novartis, we are creating the
next wave of immunocellular cancer treatments, and are eager to progress CAR-T
therapy in a host of hematologic and other cancer types."

In close collaboration with Novartis and Penn, Children''s Hospital of
Philadelphia (CHOP) was the first institution to investigate Kymriah in the
treatment of pediatric patients leading the single site trial.

"Tisagenlecleucel is the first CAR-T therapy to demonstrate early, deep and
durable remission in children and young adults with relapsed or refractory B-
cell ALL," said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of
Pediatrics at the Perelman School of Medicine at Penn, and Director of the
Cancer Immunotherapy Frontier Program at Children''s Hospital of Philadelphia
(CHOP). "We''ve never seen anything like this before and I believe this therapy
may become the new standard of care for this patient population."

Novartis is committed to ensuring eligible patients have access to Kymriah, and
is working to ensure payers understand the value of Kymriah and provide coverage
for patients. To address the unique aspects of the therapy, Novartis has also
developed various patient access programs to support safe and timely access for
patients. Novartis is also providing traditional support to patients by helping
them navigate insurance coverage and providing financial assistance for those
who are uninsured or underinsured.

Novartis plans additional filings for Kymriah in the US and EU later this year,
including applications with the FDA and European Medicines Agency (EMA), for the
treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL).
Additional filings beyond the US and EU are anticipated in 2018.

Groundbreaking Collaboration with the Centers for Medicare and Medicaid Services
Novartis also announced a novel collaboration with the United States Centers for
Medicare and Medicaid Services (CMS) focused on improving efficiencies in
current regulatory requirements in order to deliver value-based care and ensure
access for this specific patient population.

This approach is intended to include indication-based pricing for medicines and
supports payments for a medicine, such as Kymriah for its initial indication,
based on the clinical outcomes achieved, which would eliminate inefficiencies
from the healthcare system. Other value-based approaches related to future
indications for Kymriah and CAR-T cell therapies are under discussion.

Furthermore, Novartis is collaborating with CMS to make an outcomes-based
approach available to allow for payment only when pediatric and young adult ALL
patients respond to Kymriah by the end of the first month. Future potential
indications would be reviewed for the most relevant outcomes-based approach.

"Novartis has been at the forefront of outcomes-based pricing and is very
pleased to work with CMS on this first-of-its-kind collaboration with a
technology that has the potential to transform cancer care," said Joseph
Jimenez, CEO of Novartis. "We look forward to continuing to work with CMS to
potentially expand this approach to other products and disease states."

About Kymriah Manufacturing
Kymriah will be manufactured for each individual patient using their own cells
at the Novartis Morris Plains, New Jersey facility. Novartis has designed a
reliable and integrated manufacturing and supply chain platform that allows for
an individualized treatment approach on a global scale. This process includes
cryopreservation of a patient''s harvested (or leukapheresed) cells, giving
treating physicians and centers the flexibility to initiate therapy with Kymriah
based on the individual patient''s condition. Building on our experience, having
manufactured CAR-T cells for over 250 patients from 11 countries across various
indications, we have demonstrated a reproducible product. Novartis continues to
advance its CAR-T manufacturing expertise in Morris Plains, where we have been
supplying CAR-T cells for global clinical trials and where we continue to invest
in support of the anticipated demand to meet the needs of patients.

Kymriah Pivotal Study Results
The FDA approval of Kymriah is based on the results of the pivotal open-label,
multicenter, single-arm Phase II ELIANA trial, the first pediatric global CAR-T
cell therapy registration trial examining patients in 25 centers in the US, EU,
Canada, Australia and Japan. In this Novartis-sponsored study, 68 patients were
infused and 63 were evaluable for efficacy. Results show 83% (52 of 63; 95%
confidence interval [CI]: 71%-91%) of patients who received treatment with
Kymriah achieved complete remission (CR) or CR with incomplete blood count
recovery (CRi) within three months of infusion. In addition, no minimal residual
disease (MRD) - a blood marker that indicates potential relapse - was detected
among responding patients. Median duration of remission was not reached (95% CI:
7.5-NE) [1].

The most common (>20%) adverse reactions in the ELIANA trial are cytokine
release syndrome (CRS), hypogammaglobulinemia, infections-pathogen unspecified,
pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding
episodes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders,
hypoxia, fatigue, acute kidney injury and delirium. In the study, 49% of
patients treated with Kymriah experienced grade 3 or 4 CRS, an on-target effect
of the treatment that may occur when the engineered cells become activated in
the patient''s body. CRS was managed globally using prior site education and
implementation of the CRS treatment algorithm. Within eight weeks of treatment,
18% of patients experienced grade 3 or 4 neurologic events. There were no
incidents of cerebral edema. The most common neurologic events were
encephalopathy (34%), headache (37%), delirium (21%), anxiety (13%) and tremor

Novartis Leadership in Immuno-Oncology
Novartis is at the forefront of investigational immunocellular therapy and was
the first pharmaceutical company to significantly invest in CAR-T research, work
with pioneers in CAR-T and initiate global CAR-T trials. Kymriah, the first
approved CAR-T cell therapy, is the cornerstone of this strategy. Active
research programs are underway targeting other hematologic malignancies and
solid tumors, and include efforts focused on next generation CAR-Ts that involve
simplified manufacturing schemes and gene edited cells.

In April 2017, the FDA granted Breakthrough Therapy designation to CTL019 based
on data from the JULIET study, the first multi-center global registration study
for CTL019 in adult patients with r/r DLBCL.

About ALL
ALL is a cancer of the lymphocytes, a type of white blood cell involved in the
body''s immune system. In people with ALL, the abnormal cells crowd other types
of cells in the bone marrow, preventing the production of red blood cells (which
carry oxygen), other types of white blood cells and platelets (parts of the
blood needed for clotting). As a result, those with ALL may be anemic, more
likely to get infections and bruise or bleed easily [4].

ALL comprises approximately 25% of cancer diagnoses among children under 15
years old and is the most common childhood cancer in the US [5]. Despite overall
improvements in outcomes of pediatric/young adult B-cell ALL, effective
treatment options for patients that have relapsed or are refractory to treatment
are limited [6],[7],[8].

Kymriah(TM) (tisagenlecleucel) Important Safety information
The full prescribing information, including Boxed WARNING, for Kymriah can be
found at:

Kymriah may cause side effects that are fatal or life-threatening, such as
Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS
may experience symptoms including high fever, difficulty breathing,
chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or
joint pain, very low blood pressure or dizziness/lightheadedness. Patients may
be admitted to the hospital for CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or
decreased consciousness, headaches, delirium, confusion, agitation, anxiety,
seizures, difficulty speaking and understanding, or loss of balance. Patients
should be advised to call their health care provider or get emergency help right
away if they experience any of these signs and symptoms of CRS or neurological

Because of the risk of CRS and neurological toxicities, Kymriah is only
available through a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah
infusion. Kymriah can increase the risk of life-threatening infections that may
lead to death. Patients should be advised to tell their health care provider
right away if they develop fever, chills, or any signs or symptoms of an

Patients may experience prolonged low blood cell counts (cytopenia), where one
or more types of blood cells (red blood cells, white blood cells, or platelets)
are decreased. The patient''s health care provider will do blood tests to check
all of their blood cell counts after treatment with Kymriah. Patients should be
advised to tell their health care provider right away if they get a fever, are
feeling tired, or have bruising or bleeding.

Patients may experience hypogammaglobulinemia, a condition in which the level of
immunoglobulins (antibodies) in the blood is low and the risk of infection is
increased. It is expected that patients may develop hypogammaglobulinemia with
Kymriah, and may need to receive immunoglobulin replacement for an indefinite
amount of time following treatment with Kymriah. Patients should tell their
health care provider about their treatment with Kymriah before receiving a live
virus vaccine.

After treatment with Kymriah, patients will be monitored life-long by their
health care provider, as they may develop secondary cancers or recurrence of
their leukemia.

Patients should not drive, operate heavy machinery, or do other dangerous
activities for 8 weeks after receiving Kymriah because the treatment can cause
temporary memory and coordination problems, including sleepiness, confusion,
weakness, dizziness and seizures.

Some of the most common side effects of Kymriah included: difficulty breathing,
fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea,
vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and
dizziness/lightheadedness. However, these are not all of the possible side
effects of Kymriah. Patients should talk to their health care provider for
medical advice about side effects.

Prior to a female patient starting treatment with Kymriah, their health care
provider may do a pregnancy test. There is no information available for Kymriah
use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended
for women who are pregnant or breast feeding. If either sex partner has received
Kymriah, patients should talk to their health care provider about birth control
and pregnancy.

Patients should tell their health care provider about all the medicines they
take, including prescription and over-the-counter medicines, vitamins, and
herbal supplements.

After receiving Kymriah, patients should be advised that some commercial HIV
tests may cause a false positive test result. Patients should also be advised
not to donate blood, organs, or tissues and cells for transplantation after
receiving Kymriah.

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 "pioneering,"
"commitment," "breakthrough," "mission," "is establishing," "will,"
"investigational," "step forward," "may," "are creating," "next wave," "eager to
progress," "committed," "is working to," "plans," "later this year,"
"anticipated," "would," "under discussion," "potential," "look forward to,"
"potentially," "strategy," "underway," "efforts," "focused on," "next
generation," "continues to advance," "continue to invest," "Breakthrough Therapy
designation," or similar terms, or by express or implied discussions regarding
potential marketing approvals, new indications or labeling for Kymriah and the
other investigational products described in this press release, regarding our
ability to implement, scale and sustain commercial manufacturing for Kymriah or
the other investigational products described in this press release, regarding
our ability to build a network of treatment centers to offer Kymriah or the
other investigational products described in this press release, regarding the
potential future success of patient support programs or patient access solutions
for Kymriah or of the collaboration with CMS to establish indication-based
pricing and outcomes-based payments for CAR-T cell therapies, 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 Kymriah or the other
investigational 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. Neither can there be any guarantee that Novartis will
secure continued approval for Kymriah or the other investigational products
described in this press release following accelerated approval. Nor can there be
any guarantee that Novartis will successfully implement, scale and sustain
commercial manufacturing for Kymriah or the other investigational products
described in this press release, or successfully build a network of treatment
centers to offer Kymriah or the other investigational products described in this
press release. Neither can there be any guarantee that Novartis will
successfully implement patient support programs or patient access solutions for
Kymriah or the other investigational products described in this press release,
or that the collaboration with CMS to establish indication-based pricing and
outcomes-based payments for CAR-T cell therapies will be successful or achieve
its intended goals. Nor can there be any guarantee that Kymriah or the other
investigational products described in this press release will be commercially
successful in the future. In particular, our expectations regarding Kymriah and
such other investigational products could be affected by, among other things,
our ability to successfully implement, scale and sustain commercial
manufacturing and build a network of treatment centers; our ability to
successfully implement patient support programs and patient access solutions;
our ability to secure continued approval following accelerated approval; our
ability to successfully establish indication-based pricing and outcomes-based
payments for CAR-T cell therapies in collaboration with CMS; 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; our ability to obtain or maintain proprietary
intellectual property protection; the particular prescribing preferences of
physicians and patients; global trends toward health care cost containment,
including government, payor and general public pricing and reimbursement
pressures; general economic and industry conditions, including the effects of
the persistently weak economic and financial environment in many countries;
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,
cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has
leading positions globally in each of these areas. In 2016, the Group achieved
net sales of USD 48.5 billion, while R&D throughout the Group amounted to
approximately USD 9.0 billion. Novartis Group companies employ approximately
119,000 full-time-equivalent associates. Novartis products are sold in
approximately 155 countries around the world. For more information, please visit

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[1] Kymriah (tisagenlecleucel) Prescribing information. East Hanover, New
Jersey, USA: Novartis Pharmaceuticals Corporation; August 2017.
[2] Ronson, A., Tvito, A., Rowe, JM., "Treatment of Relapsed/Refractory Acute
Lymphoblastic Leukemia in Adults." Current Oncology Reports, 2016 Jun;18(6):39. Accessed August 4, 2017.
[3] Leukemia & Lymphoma Society, "Acute Lymphoblastic Leukemia."
and-refractory. Accessed August 4, 2017.
[4] National Cancer Institute, "Childhood Acute Lymphoblastic Leukemia Treatment
(PDQ®) - Patient Version."
all-treatment-pdq#link/_1. Accessed August 4, 2017.
[5] Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer Statistics
Review, 1975-2010. National Cancer Institute, April 2013; Section 28.9 (12).
[6] Oudot, C.., Auclerc, F.., Levy, V., et al. Prognostic Factors for Leukemia
Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome
After Salvage Therapy: The FRALLE 93 Study. Journal of Clinical Oncology, March
2008; Volume 28 (9).
[7] Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed
childhood acute lymphoblastic leukaemia. British Journal of Hematology,
2003; 123 (3).
[8] Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and
adolescents with a second or third relapse of acute lymphoblastic leukemia
(ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-
Münster) Study Group. Journal of Pediatric Hematology/Oncology. July 2013; 35

# # #

Novartis Media Relations
Central media line: +41 61 324 2200
E-mail: media.relations(at)

Eric Althoff Fiona Phillips
Novartis Global Media Relations Novartis Oncology Communications
+41 61 324 7999 (direct) +1 862-778-7705 (direct)
+41 79 593 4202 (mobile) +1 862-217-9396 (mobile)
eric.althoff(at) fiona.phillips(at)

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations(at)

Central   North America

Samir Shah +41 61 324 7944 Richard Pulik +1 212 830 2448

Pierre-Michel Bringer +41 61 324 1065 Cory Twining +1 212 830 2417

Thomas Hungerbuehler +41 61 324 8425

Isabella Zinck +41 61 324 7188

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Date: 08/30/2017 - 17:04
Language: English
News-ID 1519290
Character count: 2227
Firma: Novartis International AG
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Stadt: Basel


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