-
Filing acceptance marks second
Priority Review granted to Kymriah by the FDA for two distinct
indications, underscoring the potential of first ever FDA-approved
CAR-T therapy
-
EMA granted accelerated
assessment to Kymriah for children, young adults with r/r B-cell
ALL and adults with r/r DLBCL who are ineligible for autologous
stem cell transplant
-
Novartis is working closely
with the FDA and EMA to make Kymriah available to more patients
with critical unmet need
Basel, January 17, 2018
- Novartis today announced that its
supplemental Biologics License Application (sBLA) for
KymriahTM
(tisagenlecleucel) suspension for intravenous infusion, formerly
CTL019, for the treatment of adult patients with relapsed or
refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who are
ineligible for or relapse after autologous stem cell transplant
(ASCT) has been accepted by the US Food and Drug Administration
(FDA) for Priority Review. In addition, the European Medicines
Agency (EMA) has granted accelerated assessment to the Marketing
Authorization Application (MAA) for Kymriah for the treatment of
children and young adults with r/r B-cell acute lymphoblastic
leukemia (ALL) and for adult patients with r/r DLBCL who are
ineligible for ASCT. Priority Review and accelerated assessment are
granted to therapies which may provide a significant improvement in
the safety and effectiveness of the treatment of a serious disease,
and the designations are intended to expedite the standard review
time. If approved by the FDA and EMA, Kymriah would represent the
first chimeric antigen receptor T cell (CAR-T) therapy available
for two distinct indications in non-Hodgkin lymphoma and B-cell
ALL.
Kymriah became the first CAR-T cell therapy to
receive regulatory approval when it was approved by the FDA in
August 2017 for the treatment of patients up to 25 years of age
with B-cell precursor ALL that is refractory or in second or later
relapse.
"The first approval of a CAR-T therapy truly
redefined the future of the cancer treatment landscape, and we are
only at the beginning of this new era in cancer care," said Samit
Hirawat, MD, Head, Novartis Oncology Global Drug Development. "The
Priority Review designation and accelerated assessment signal that
the FDA and EMA have recognized the potential of Kymriah to provide
a much-needed therapeutic option for these patients with relapsed
or refractory B-cell ALL and DLBCL. We are now focused on working
with these regulatory agencies to bring this potentially
transformative therapy to more patients."
Kymriah is a novel immunocellular therapy and a
one-time treatment that uses a patient's own T cells to fight
cancer. 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.
The regulatory applications in the US and EU are
based on data from the Novartis-sponsored global clinical trial
program of Kymriah in children and young adults with r/r B-cell ALL
and adult patients with r/r DLBCL demonstrating the efficacy and
safety of Kymriah across studies. Results from the pivotal phase II
JULIET clinical trial served as the basis of the sBLA and MAA
(applications submitted by pharmaceutical companies to health
authorities when seeking approval of a new product) for Kymriah in
adult patients with r/r DLCBL. Results from the pivotal phase II
ELIANA study were submitted as part of the MAA for Kymriah in
children and young adults with r/r B-cell ALL.
JULIET is the first multi-center global
registration study for Kymriah in adult patients with r/r DLBCL.
JULIET is the largest study examining a CAR-T therapy in DLBCL,
enrolling patients from 27 sites in 10 countries across the US,
Canada, Australia, Japan and Europe, including: Austria, France,
Germany, Italy, Norway and the Netherlands. Data from the six-month
primary analysis of JULIET were presented at the annual meeting of
the American Society of Hematology (ASH) in December 2017.
ELIANA is the first pediatric global CAR-T cell
therapy registration trial, examining patients in 25 centers in the
US, Canada, Australia, Japan and the EU, including: Austria,
Belgium, France, Germany, Italy Norway, and Spain.
Novartis plans additional regulatory submissions
for Kymriah in pediatric and young adult patients with r/r B-cell
ALL and adult patients with r/r DLBCL beyond the US and EU in
2018.
About CAR-T
CAR-T is different from typical small molecule or biologic
therapies because it is manufactured for each individual patient
using their own cells. During the treatment process, T cells are
drawn from a patient's blood and reprogrammed in the laboratory to
create T cells that are genetically coded to recognize and fight
the patient's cancer cells and other B cells expressing a
particular antigen.
About Kymriah
Manufacturing
Kymriah is manufactured for each individual patient using their own
cells at the Novartis Morris Plains, New Jersey facility. In the
US, the target turnaround time for manufacturing Kymriah in the
commercial setting is 22 days. The reliable and integrated
manufacturing and supply chain platform for Kymriah allows for an
individualized treatment approach on a global scale. The 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 the company's
experience, having manufactured CAR-T cells for over 300 patients
from 11 countries across various indications in clinical trials, it
has 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.
Novartis has also successfully established the
CTL019 manufacturing process at the Fraunhofer-Institut for cell
therapy and immunology (Fraunhofer-Institut für Zelltherapie and
Immunologie) facility in Leipzig, Germany, which currently supports
the manufacturing of CTL019 for global clinical trials.
Novartis Leadership in
Immuno-Oncology
Novartis is at the forefront of investigational immunocellular
therapy as the first pharmaceutical company to initiate global
CAR-T trials, and has significantly invested in CAR-T research and
worked with pioneers in the field. KymriahTM, 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.
KymriahTM
(tisagenlecleucel) US Important Safety
information (for patients up to 25 years of age with B-cell
precursor ALL that is refractory or in second or later
relapse)
The full prescribing information, including Boxed WARNING, for
Kymriah can be found at:
https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf
Kymriah may cause side effects that are severe 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 toxicities.
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) in the US
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 infection.
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
are 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.
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," "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, regarding our
ability to implement, scale and sustain commercial manufacturing
for the investigational or approved products described in this
press release, regarding our ability to build and sustain a network
of treatment centers to offer 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. Neither can there be any guarantee that Novartis
will successfully implement, scale and sustain commercial
manufacturing for the investigational or approved products
described in this press release, or successfully build and sustain
a network of treatment centers to offer the investigational or
approved products described in this press release. 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, our ability to
successfully implement, scale and sustain commercial manufacturing
and build and sustain a network of treatment centers; 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 121,000 full-time-equivalent
associates. Novartis products are sold in approximately 155
countries around the world. For more information, please visit
http://www.novartis.com.
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