(NHL). Management anticipates the completion of the BLA submission by the end
of first-quarter 2017 and launching the new
medicine for NHL in 2017.
The drug compound has been granted
Breakthrough Therapy Designation status
for diffuse large B-cell lymphoma (DLBCL),
transformed follicular lymphoma (TFL),
and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. FDA and Priority
Medicines (PRIME) regulatory support for
DLBCL in the European Union. Kite is planning a regulatory submission to the European Medicines Agency during 2017.
“We are making history with each step we
take toward bringing engineered T-cell therapy to patients,” says Arie Belldegrun, M.D.,
FACS, Chairman, President, and CEO of Kite.
During January 2017, Kite and Shanghai
Fosun Pharmaceutical (Group) Co. Ltd. announced a joint venture, Fosun Pharma Kite
Biotechnology Co. Ltd. The joint venture will
develop, manufacture and commercialize
axicabtagene ciloleucel in China with the option to include additional products, including
two T cell receptor (TCR) product candidates
from Kite. Fosun Pharma Kite will initially
concentrate on axicabtagene ciloleucel. The
joint venture has the option to license additional product candidates such as KITE-439,
a TCR therapy directed against the human
papillomavirus type 16 E7 oncoprotein and
KITE-718, a TCR therapy directed against
MAGE A3 and MAGE A6, antigens frequently found in solid tumors including bladder,
esophageal, head and neck, lung and ovarian cancers. Opt-in and milestone payments
for KITE-439 and KITE-718 could amount
to ;140 million plus profit sharing as well as
mid-single digit sales royalties.
Kite announced that characterizations
of T cell receptor candidates which it has licensed under the Cooperative Research and
Development Agreement (CRADA) with the
National Institutes of Health (NIH) were
published in the Dec. 8, 2016, New England
Journal of Medicine (NEJM). The research
– led by Steven A. Rosenberg, M.D., Ph.D.,
chief of the Surgery Branch at NCI’s Center
for Cancer Research and a scientific collaborator with Kite – describes a patient with
KRAS mutant metastatic colorectal cancer
who was successfully treated with T cells that
are reactive to KRAS G12D mutation. According to Kite, this work follows previously
reported treatment of a patient with advanced cholangiocarcinoma with T cells targeting a mutated erbb2 interacting protein.
As published in the NEJM publication,
mutations in the KRAS gene are believed
to drive 95 percent of all pancreatic cancers
and 45 percent of all colorectal cancers. The
G12D mutation is the most common KRAS
mutation and is estimated to take place in
more than 50,000 new cases of cancer in
the United States annually.
Kite announced during September 2016
that it had entered into an exclusive, world-
wide license with the NIH for intellectual
property related to multiple TCR-based
product candidates for the treatment of tu-
mors expressing mutated KRAS antigens.
These TCR product candidates were devel-
oped in the laboratories of Dr. Rosenberg
and James C. Yang, M.D., of the NCI.
During the third quarter of 2016, Kite
initiated patient enrollment in a Phase 1b;2
combination study of KTE-C19 and Genentech’s anti-PD-L1 monoclonal antibody
atezolizumab. This represents the first combination trial of an anti-CD19 engineered
CAR T-cell and a checkpoint inhibitor.
At Kite’s investor day on Oct. 18, 2016,
the company outlined KTE-C19 expansion
studies with the potential to deliver six additional indications in B-cell malignancies.
Also announced was the expansion of Kite’s
TCR and CAR T development pipeline with
four new INDs planned in the 2016-2018
timeframe. In addition, presented were “T
cells 2.0” next-generation cell programming
technologies to realize the full potential of
engineered T-cell therapy.
Novartis possesses one of the industry’s most respected development pipe- lines, with more than 200 projects in
clinical development as of year-end 2016. The
company has 14 different pipeline projects
expected to be filed for regulatory approval
during 2017, including three new molecular
entities; AMG334 for migraine, CTL019 for
pediatric acute lymphoblastic leukemia, and
RL;030 for acute heart failure.
The fully human monoclonal antibody
AMG334;erenumab is specifically designed
to target and block the calcitonin gene-relat-ed peptide (CGRP) receptor, believed to have
a critical role in mediating the incapacitating
pain of migraine. Following the initial Phase
II dose finding study in the prevention of episodic migraine, the efficacy of AMG 334 in
migraine prevention has been demonstrated
in a Phase II trial in chronic migraine and
two Phase III studies in episodic migraine.
AMG 334 is being evaluated in several large
global, randomized, double-blind, place-
bo-controlled studies to assess its safety and
efficacy in migraine prevention. AMG 334 is
being jointly developed by Novartis and Am-
gen. The companies are pursuing discussions
with regulatory agencies for potential ap-
proval submissions in respective territories.
Amgen holds commercialization rights in the
U.S., Canada, and Japan. Novartis maintains
commercialization rights in Europe and the
rest of the world.
Novartis entered into a worldwide collaboration with Amgen during August 2015
to jointly develop and commercialize pioneering neuroscience treatments in the area
of Alzheimer’s disease and migraine. The
companies are partners in the development
and commercialization of a beta-secretase 1
(BACE) inhibitor program in AD. Novartis’
oral therapy CNP520 – undergoing a Phase II
trial for AD – is the lead molecule and further
compounds from both companies’ pre-clinical BACE inhibitor programs may be considered as novel follow-on molecules. CNP520
has received FDA fast track designation. The
collaboration additionally focuses on innovative investigational Amgen drugs in the
migraine category, including AMG 334 (in
Phase III studies for episodic migraine as well
as open-label studies in episodic and chronic
migraine) and AMG 301 (in a Phase I study).
Novartis in December presented results
from the first global registration study of
CTL019 in pediatric and young adult patients with relapsed;refractory (r;r) pediatric
and young adult patients with B-cell acute
lymphoblastic leukemia (ALL). Eighty-two
percent ( 41 of 50) of patients achieved complete remission or complete remission with
incomplete blood count recovery in interim
analysis of the Novartis trial called ELIANA.
CTL019 is an investigational chimeric antigen receptor T cell (CAR T) therapy.
Study enrollment has taken place across
25 centers in the United States, EU, Canada,
Australia and Japan. The first global CAR T
cell study, ELIANA will form the basis of a
biologics licensing application to the FDA
during early 2017. Novartis pivotal data from
ELIANA is supported by the CTL019 U.S.
multicenter study ENSIGN as well as an earlier single site trial in r;r pediatric and young
adult patients with B-cell ALL. Novartis also
intends to submit for approval with the European Medicines Agency (EMA) later in 2017.
Industry analysts are abuzz over LEE011
(ribociclib) in combination with letrozole
as first-line treatment for postmenopausal women with HR;;HER2- advanced or
metastatic breast cancer. FDA has granted
Priority Review to the new drug, and the
EMA also has accepted for review the Novartis application for LEE011 plus letrozole
in the same patient population.
Analyses from the Phase III MONA-
LEESA-2 trial demonstrated that LEE011
plus letrozole significantly prolonged pro-
gression-free survival across various pre-
planned patient subgroups with HR;;
HER2- advanced or metastatic breast can-
cer, including post-menopausal women di-
agnosed de novo, those with visceral metas-
tases, and those with bone-only disease.
Novartis is continuing to study LEE011
through the robust MONALEESA (Mamma-
ry ONcology Assessment of LEE011’s Effica-
cy and SAfety) clinical trial program, which
includes MONALEESA-2, MONALEESA- 3,
and MONALEESA- 7. These studies are as-
sessing LEE011 in multiple endocrine therapy
combinations across a wide range of patients,
including men and premenopausal women.
LEE011 (ribociclib) is a selective cyclin de-
pendent kinase inhibitor, a class of drugs that
aid in slowing the progression of cancer by
inhibiting two proteins called cyclin depen-
dent kinase 4 and 6 (CDK4; 6). These pro-
teins, when over-activated in a cell, can allow
cancer cells to grow and divide too rapidly.
Research shows that targeting CDK4; 6 with
enhanced precision may play a role in ensur-
ing cancer cells do not grow uncontrollably.
As of this magazine’s press time, LEE011
had not been approved for any indication in
any market worldwide. LEE011 was devel-
oped by the Novartis Institutes for BioMed-
ical Research (NIBR) via a research collabo-
ration with Astex Pharmaceuticals.
Novartis announced in November that
FDA had granted priority review to PKC412
(midostaurin) for treating newly diagnosed
FLT3 mutation-positive acute myeloid leukemia and advanced systemic mastocytosis.
The Priority Review for the new drug application was based on data from the largest
clinical studies ever performed for each indication. The EMA additionally has accepted the PKC412 (midostaurin) submission
With the AML treatment strategy having remained unchanged for more than
25 years, PKC412 may represent the first
FLT3-mutated AML drug with a survival
benefit. The investigational, oral, multi-tar-geted kinase inhibitor is intended for the
treatment of patients with AML with a FLT3
mutation and for patients with advanced
SM. PKC412 has not yet been approved for
any indication worldwide.
Additionally known as serelaxin,
RL;030 is a recombinant form of human
relaxin-2 hormone. Undergoing Phase III
development for acute heart failure, the potential new product is administered via intravenous infusion.
Pursuing our “bolt-on” strategy to strengthen
Hepatology Dermatology Cardiovascular
1 A nnounced an agreement to acquire, subject to closing conditions
2 A nnounced an agreement to license products, subject to closing conditions
An Industry-Leading CAR/TCR Pipeline