- Priority review
for investigational CTL019 (tisagenlecleucel-T), a novel therapy
that is manufactured for each individual patient using their own T
cells
- Novartis made an
early commitment to the emerging field of CAR-T investigational
therapies through collaboration with the University of Pennsylvania
including CTL019
- Novartis plans
to submit an application for market authorization with the European
Medicines Agency (EMA) later this year
Basel, March 29, 2017
- Novartis announced today that the US Food
and Drug Administration (FDA) has accepted the company's Biologics
License Application (BLA) filing and granted priority review for
CTL019 (tisagenlecleucel-T), an investigational chimeric antigen
receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r)
pediatric and young adult patients with B-cell acute lymphoblastic
leukemia (ALL). This is the first BLA submission by Novartis for a
CAR-T. The priority review designation is expected to shorten the
anticipated review time by the FDA.
CAR-T is different from typical small molecule or
biologic therapies currently on the market because it is
manufactured for each individual patient. 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
hunt the patient's cancer cells and other B-cells expressing a
particular antigen.
"With CTL019, Novartis is at the forefront of the
science and development of immunocellular therapy as a potential
new innovative approach to treating certain cancers where there are
limited options," said Vas Narasimhan, Global Head of Drug
Development and Chief Medical Officer, Novartis. "The priority
review and file acceptance of CTL019 by the FDA brings us one step
closer to delivering this novel treatment option to children and
young adults with r/r B-cell ALL in the United States."
CTL019 was first developed by the University of
Pennsylvania. In 2012, Novartis and the University of Pennsylvania
entered into a global collaboration to further research, develop
and then commercialize CAR-T cell therapies for the investigational
treatment of cancers, including CTL019. Through the collaboration,
Novartis holds the worldwide rights to CARs developed through the
collaboration with the University of Pennsylvania for all cancer
indications.
"The past five years have seen tremendous progress
in the development and application of cellular engineering in an
effort to personalize the treatment of cancer," said the Penn
team's leader, Carl June, MD, director of the Center for Cellular
Immunotherapies in the Perelman School of Medicine at the
University of Pennsylvania. "We now know that it is possible to
treat patients in clinical trials across the world using this
approach, and the results we have observed mark a potential new
paradigm in the treatment of blood cancers that have not responded
to standard therapies."
The priority review designation and BLA submission for CTL019 is
based on the results from the Novartis-sponsored ELIANA study
(NCT02435849), the first global CAR-T cell trial with study
enrollment having occurred across 25 centers in the US, EU, Canada,
Australia and Japan. In the Phase II study, 82% (41 of 50) of
patients infused with CAR-T cells achieved complete remission or
complete remission with incomplete blood count recovery at three
months post CTL019 infusion. The data were presented at the
American Society of Hematology meeting in December 2016 (Abstract
#221)[1].
Forty-eight percent of patients in the ELIANA
trial experienced grade 3 or 4 cytokine release syndrome (CRS), a
known complication of an investigational therapy that may occur
when the engineered cells become activated in the patient's body.
CRS was managed per protocol on a global scale using prior site
education with implementation of the CRS treatment algorithm. There
were no deaths due to CRS. Fifteen percent of patients experienced
grade 3 neurological and psychiatric events including confusion,
delirium, encephalopathy, agitation and seizure. No cerebral edema
was reported and no grade 4 neurological and psychiatric events
were observed[1].
The submission is also supported by findings from
a US multicenter trial and an earlier single site trial led by the
Children's Hospital of Philadelphia (CHOP) examining the safety and
efficacy of CTL019 among pediatric and young adult patients with
r/r B-cell ALL. Stephan Grupp, MD, PhD, from CHOP was the lead
investigator of the trials.
"Even if a patient has difficult-to-treat
relapsed/refractory leukemia, we have seen treatment with CTL019 in
clinical trials put cancer into remission," said Grupp, Director of
the Cancer Immunotherapy Frontier Program and Director of
Translational Research for the Center for Childhood Cancer Research
at CHOP. "This could be a first-of-its-kind treatment with exciting
potential to help pediatric and young adult r/r B-cell ALL
patients."
Acute lymphoblastic leukemia makes up
approximately 25% of cancer diagnoses among children under 15 years
old and is the most common childhood cancer in the US[2]. Patients
with r/r ALL have limited treatment options, and the chance of
survival for children with the disease who relapse or fail to
attain remission is between 16% to 30%[3].
According to the FDA guidelines, Priority Review
status may potentially shorten the window for the agency to take
action on an application to within six months of the filing
acceptance compared to a standard review. The designation aims to
prioritize the evaluation of products that have the potential to
provide significant improvements in the treatment, diagnosis or
prevention of serious conditions when compared to standard
applications. CTL019 previously received Breakthrough Therapy
designation from the FDA for the treatment of patients with r/r
ALL.
Novartis plans additional filings for CTL019 in
the US and EU markets later this year, including a BLA with the FDA
for treatment of adults with r/r diffuse large B-cell lymphoma
(DLBCL) and applications for marketing authorization with the
European Medicines Agency in r/r B-cell ALL and r/r DLBCL.
Because CTL019 is an investigational therapy, the
safety and efficacy profile has not yet been established. Access to
investigational therapies is available only through carefully
controlled and monitored clinical trials. These trials are designed
to better understand the potential benefits and risks of the
therapy. Because of the uncertainty of clinical trials, there is no
guarantee that CTL019 will ever be commercially available anywhere
in the world.
Disclaimer
The foregoing release contains forward-looking
statements that can be identified by words such as "priority
review," "commitment," "investigational," "plans," "expected,"
"potential," "possible," "may," "could," "potentially," "aims to,"
"designed to," "will," or similar terms, or by express or implied
discussions regarding potential additional filings or potential
marketing approvals for CTL019, or regarding potential future
revenues from CTL019. 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 CTL019
will be submitted or approved for sale in any market, or at any
particular time. Nor can there be any guarantee that CTL019 will be
commercially successful in the future. In particular, management's
expectations regarding CTL019 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; 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; 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 118,000
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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References
[1] Grupp, Stephan A. et al. Analysis of a Global
Registration Trial of the Efficacy and Safety of CTL019 in
Pediatric and Young Adults with Relapsed/Refractory Acute
Lymphoblastic Leukemia (ALL). Session 614, Saturday, December 3,
5:00 p.m. PST. 58th American Society of Hematology Annual Meeting
and Exposition: Abstract 221.
[2] Howlader, N., Noone, A. M., Krapcho, M, et al. SEER Cancer
Statistics Review, 1975-2010. National Cancer Institute, April
2013; Section 28.9 (12).
http://www.seer.cancer.gov/csr/1975_2010/results_merged/sect_28_childhood_cancer.pdf.
Accessed March 2017.
[3] Satwani, P. MD, et al. Allogenic Bone Marrow Transplantation in
First Remission for Children With Ultra-High-Risk Features of Acute
Lymphoblastic Leukemia: A Children's Oncology Group Study Report.
Biol Blood Marrow Transplant, February 2007; 13(2): 218-227.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731715/. Accessed
March 2017.
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