-
Recommendation based on review
of CTL019 r/r B-cell ALL development program, including the pivotal
Phase II global ELIANA trial
-
A Biologics License Application
(BLA) for this indication is under FDA priority review; if
approved, CTL019 could become first CAR-T cell therapy
available
-
Positive ODAC recommendation is
latest milestone for CTL019 program that started through
collaboration with the University of Pennsylvania
Basel, July 12, 2017
- Novartis announced today that the US Food
and Drug Administration (FDA) Oncologic Drugs Advisory Committee
(ODAC) unanimously (10-0) recommended approval of CTL019
(tisagenlecleucel), an investigational chimeric antigen receptor T
cell (CAR-T) therapy, for the treatment of relapsed or refractory
(r/r) pediatric and young adult patients with B-cell acute
lymphoblastic leukemia (ALL).
"The panel's unanimous recommendation in favor of
CTL019 moves us closer to potentially delivering the first-ever
commercially approved CAR-T cell therapy to patients in need," said
Bruno Strigini, CEO, Novartis Oncology. "We're very proud to be
expanding new frontiers in cancer treatment by advancing
immunocellular therapy for children and young adults with r/r
B-cell ALL and other critically ill patients who have limited
options. We look forward to working with the FDA as they complete
their review."
Acute lymphoblastic leukemia comprises
approximately 25% of cancer diagnoses among children under 15 years
old and is the most common childhood cancer in the US[1]. Effective
treatment options for patients with r/r ALL are limited. In
pediatric and young adult patients with B-cell ALL that have
relapsed multiple times or become refractory to treatment, the
five-year disease-free survival is less than 10-30%[2],[3],[4].
The ODAC recommendation is based on review of the
CTL019 r/r B-cell ALL development program, which includes the
Novartis-led ELIANA study (NCT02435849), the first pediatric global
CAR-T cell therapy registration trial. Findings from a US
multicenter trial and a single site trial examining the safety and
efficacy of CTL019 among pediatric and young adult patients with
r/r B-cell ALL also supported the recommendation and the Biologics
License Application (BLA)[5].
CTL019 was first developed by the University of
Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its
chimeric antigen receptor to enhance cellular responses as well as
persistence of CTL019 after it is infused into the patient, which
may be associated with long-lasting remissions in patients. In
2012, Novartis and Penn entered into a global collaboration to
further research, develop and commercialize CAR-T cell therapies,
including CTL019, for the investigational treatment of cancers.
Children's Hospital of Philadelphia (CHOP) was the first
institution to investigate CTL019 in the treatment of pediatric
patients and led the single site trial.
"It is encouraging to see the FDA panel's
recommendation and continued momentum behind this innovative
therapy, which has potential to help young patients with
relapsed/refractory B-cell ALL," said the Penn team's leader, Carl
June, MD, the Richard W. Vague Professor of Immunotherapy, director
of the Center for Cellular Immunotherapies in Penn's Perelman
School of Medicine and director of the Parker Institute for Cancer
Immunotherapy at Penn. "We look forward to continuing to work with
Novartis to help make a lasting impact on the way this disease is
treated."
"We know firsthand from treating children and
young adults with relapsed/refractory B-cell ALL that they
desperately need innovative medicines that provide a new approach
to managing this aggressive disease," said Stephan Grupp, MD, PhD,
the Yetta Deitch Novotny Professor of Pediatrics at the Perelman
School of Medicine at Penn, Director of the Cancer Immunotherapy
Frontier Program and Chief of the Section of Cellular Therapy and
Transplant at CHOP. "Today's vote in favor of CTL019 is a positive
step and we appreciate Novartis' commitment to pediatric
patients."
Earlier this year, Novartis submitted a BLA for
CTL019 to the FDA, marking the first submission by Novartis for a
CAR-T cell therapy. CTL019 previously received FDA Breakthrough
Therapy designation and is under Priority Review by the FDA. The
FDA will consider the vote as it reviews the BLA, although it is
not obligated to follow the recommendation. Novartis continues to
invest in the necessary infrastructure for the potential
commercialization of CTL019, including manufacturing and the
establishment of a network of certified treatment centers.
Novartis plans additional filings for CTL019 in
the US and EU later this year, including applications with the FDA
and European Medicines Agency (EMA) for the treatment of adults
with r/r diffuse large B-cell lymphoma (DLBCL).
About CAR-T and
CTL019
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 manufacturing
facility to create T cells that are genetically coded to express a
chimeric antigen receptor to recognize and fight cancer cells and
other B-cells expressing a specific antigen.
ELIANA (NCT02435849) is the first pediatric global
CAR-T cell therapy registration trial, with study enrollment having
occurred across 25 centers in the US, Canada, EU, Australia and
Japan.
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.
About CTL019
Manufacturing
The Novartis leukapheresis process using cryopreservation allowed
for manufacturing and treatment of patients from around the world.
Cryopreserved leukapheresis involves removing white blood cells
from a patient's blood and preserving them at very low
temperatures. Cryopreserved leukapheresis gives physicians the
flexibility to schedule apheresis at a time that is in the best
interest of their patients. Novartis commercial manufacturing for
CTL019 continues to build on its experience in its Morris Plains,
New Jersey facility, which has already manufactured CTL019 for
hundreds of patients in global clinical trials. Novartis believes
that experience is important in cell therapy manufacturing, and the
experience gained at the Morris Plains, New Jersey facility will be
a foundation for commercial manufacturing of CAR-T therapies.
Novartis has made and continues to make investments in
manufacturing.
Disclaimer
This press release contains forward-looking statements, including
"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 CTL019 and the other investigational
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 CTL019
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 successfully implement and maintain commercial manufacturing
for CTL019 or the other investigational products described in this
press release, or successfully build a network of treatment centers
to offer CTL019 or the other investigational 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, 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
successfully implement and maintain commercial manufacturing and
build a network of treatment centers; 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 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.
Novartis is on Twitter. Sign up to follow
@Novartis at http://twitter.com/novartis and @Novartis Cancer at
http://twitter.com/novartiscancer.
For Novartis multimedia content, please visit
www.novartis.com/news/media-library
For questions about the site or required registration, please
contact media.relations@novartis.com
References
[1] Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer
Statistics Review, 1975-2010. National Cancer Institute, April
2013; Section 28.9 (12).
[2] 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).
[3] 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).
[4] 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 (5).
[5] Novartis CTL019 ODAC Briefing Document.
# # #
Novartis Media
Relations
Central media line: +41 61 324 2200
E-mail: media.relations@novartis.com
Eric
Althoff
Novartis Global Media Relations
+41 61 324 7999 (direct)
+41 79 593 4202 (mobile)
eric.althoff@novartis.com |
Fiona
Phillips
Novartis Oncology Communications
+1 862-778-7705 (direct)
+1 862-217-9396 (mobile)
fiona.phillips@novartis.com |
Novartis Investor
Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com
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 |
|
|
Media release (PDF)