16 • MED AD NEWS FEBRUARY 2018
the company’s existing center of excellence for immuno-oncology translational medicine by leveraging Juno’s R&D facility in Seattle as well as Juno’s
manufacturing facility in Bothell, Was.
In addition to the pivotal-stage asset JCAR017,
Juno’s JCARH125 will enhance Celgene’s campaign against BCMA (B-cell maturation antigen),
a key target in multiple myeloma. Celgene also
acquired other cellular therapy assets in proof-of-concept trials for hematologic malignancies and
Celgene’s other announced acquisition in January was the purchase of Impact Biomedicines.
The privately held biotechnology company is developing fedratinib, a highly selective JAK2 kinase
inhibitor, for myelo;brosis and polycythemia vera.
Celgene agreed to pay $1.1 billion upfront and
up to $1.25 billion in contingent payments based
on regulatory approval milestones for myelo;brosis. Additional future payments for regulatory
approvals in other indications and sales-based
milestones are additionally possible. This acquisition is expected to bolster Celgene’s commitment to myelo;brosis, a disease with high unmet
medical need, and expand strategic development
options within Celgene’s myeloid portfolio of assets. The transaction is anticipated to close during
Fedratinib was studied in 877 patients across 18
clinical trials. In a randomized, placebo-controlled,
phase III pivotal trial (JAKARTA-1) for patients
with treatment-naïve myelo;brosis, fedratinib
showed statistically signi;cant improvements in
the primary and secondary endpoints of splenic
response and total symptom score. A multi-center,
single-arm phase II study (JAKARTA- 2) assessed fedratinib in myelo;brosis patients who were found
to be resistant or intolerant to the JAK1/JAK2 inhibitor ruxolitinib (marketed as Jaka;). Based on
the reported bene;t risk pro;le of fedratinib from
the JAKARTA-1 and JAKARTA- 2 studies, regulatory
submissions in myelo;brosis are planned beginning in mid-2018.
Various clinical data were presented on Celgene’s marketed and pipeline hematology assets
at the 59th American Society of Hematology (ASH)
Annual Meeting in December 2017. For example,
Celgene and partner bluebird bio presented
updated data from the phase I study assessing
bb2121 in patients with relapsed and/or refractory multiple myeloma (RRMM). During November, bb2121 was granted Breakthrough Therapy
Designation by the FDA and PRIority MEdicines
(PRIME) eligibility by the European Medicines
Agency (EMA). The pivotal KarMMa study evaluating bb2121 in RRMM was initiated in December.
Additionally at ASH, Celgene and partner Juno
Therapeutics presented updated data from the
phase I TRANSCEND trial investigating JCAR017
in patients with relapsed or refractory aggressive
non-Hodgkin lymphoma (NHL). The pivotal TRAN-
SCEND program in the U.S. with JCAR017 in dif-
fuse large B-cell lymphoma (DLBCL) is under way
and the TRANSCEND WORLD cohort is on track to
begin during ;rst-half 2018.
In other ASH highlights, Celgene and partner
Acceleron Pharma presented updated data from
ongoing phase II studies with luspatercept in patients with lower-risk myelodysplastic syndromes
(MDS). Data from the phase III MEDALIST and BELIEVE studies are expected during mid-2018. Celgene intends to initiate the phase III COMMANDS
trial with luspatercept in front-line MDS in the ;rst
half of 2018.
Updated data were presented at ASH from the
phase Ib trial studying CC-122 in combination
with obinutuzumab in patients with DLBCL, follicular lymphoma (FL) or marginal zone lymphoma
(MZL). A pivotal program with CC-122 in NHL is
planned to begin during 2018.
Updated data were revealed during ASH from
the phase I trial investigating CC-486 in combination with rituximab plus chemotherapy (R-CHOP)
in patients with DLBCL, FL or transformed lymphoma. Data from the phase III QUAZAR\ AML-001
study evaluating CC-486 as maintenance therapy
in post-induction acute myeloid leukemia (AML) is
expected during second-half 2018.
Celgene and partner Agios Pharmaceuticals reported data at ASH from the phase I trial exploring
ivosidenib or IDHIFA combined with standard induction chemotherapy ( 7+ 3 regimen) in patients
with newly diagnosed AML with an isocitrate
dehydrogenase-1 (IDH1) or isocitrate dehydroge-nase- 2 (IDH2) mutation.
In the area of In;ammation & Immunology,
Celgene during December announced that a
New Drug Application was ;led with the FDA for
ozanimod in relapsing multiple sclerosis (RMS).
The NDA was based on data from the phase III RADIANCE Part B and SUNBEAM studies evaluating
ozanimod in patients with RMS. Celgene plans
to submit a Marketing Authorization Application
(MAA) with the EMA during ;rst-quarter 2018.
According to Celgene, a robust life-cycle plan
for ozanimod is advancing and a phase III pivotal
study investigating ozanimod in Crohn’s disease
was initiated in fourth-quarter 2017. Also, the
phase III TRUE NORTH study with ozanimod in
ulcerative colitis is under way and on track to complete enrollment during the second half of 2018.
In August, the U.S. regulatory agency approved
the use of the company’s Idhifa (enasidenib) for
treating adults with relapsed or refractory acute
myeloid leukemia with an isocitrate dehydroge-nase- 2 (IDH2) mutation as detected by an FDA-approved test.
Celgene reported during third-quarter 2017
that the phase III RELIEF (n= 207) trial investigat-
ing Otezla in patients with active Behçet’s disease
achieved the primary endpoint of Area Under the
Curve (AUC) for the number of oral ulcers from
baseline through week 12. These data form the
basis of worldwide regulatory applications that
are planned starting in 2018.
The phase IIb study evaluating CELMoD compound CC-220 in patients with systemic lupus erythematosus (SLE) was initiated during third-quarter 2017.
Gilead Sciences discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The biopharma company’s mission is to advance the care
of patients su;ering from life-threatening diseases. Gilead has operations in more than 30 countries, with headquarters located in Foster City, Cali.
Gilead’s pipeline was signi;cantly bolstered
when the company in October 2017 completed
the acquisition of Kite Pharma for $11.9 billion. Kite
Pharma, now a wholly owned subsidiary of Gilead,
was included as one of the “Top 10 Pipelines” in
Med Ad News’ February 2017 annual report.
The biopharmaceutical company Kite has been
engaged in the development of innovative cancer
immunotherapies with a goal of providing rapid,
long-term, durable response and eliminating the
burden of chronic care. Kite has concentrated on
chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered cell therapies designed to
empower the immune system’s ability to recognize and kill tumors. Kite’s lead pipeline product
and projected blockbuster brand Yescarta, which
was developed based on such technology, was
granted FDA marketing clearance in October 2017
Yescarta (axicabtagene ciloleucel, or axi-cel)
won FDA approval as the ;rst CAR T therapy for
treating adults with relapsed or refractory large
B-cell lymphoma after two or more lines of systemic therapy, including di;use large B-cell lymphoma (DLBCL) not otherwise speci;ed, primary
mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL arising from
follicular lymphoma (transformed follicular lymphoma, or TFL). CAR T therapy is a breakthrough in
hematologic cancer treatment in which a patient’s
own T cells are engineered to seek and eliminate
cancer cells. CAR T therapy is manufactured specifically for every individual patient.
The CD19-directed genetically modi;ed autologous T cell immunotherapy Yescarta is indicated
as a treatment for adult patients with relapsed
or refractory large B-cell lymphoma after two or
more lines of systemic therapy, including DLBCL
not otherwise speci;ed, primary mediastinal large
B-cell lymphoma, high-grade B-cell lymphoma,
and DLBCL arising from follicular lymphoma.
Kite announced during July 2017 the ;ling of a
Marketing Authorization Application to the European Medicines Agency for axi-cel as a treatment
for patients with relapsed/refractory DLBCL, TFL,
and PMBCL who are ineligible for autologous stem
cell transplant. Yescarta was granted Priority Medicines (PRIME) regulatory support for DLBCL in the
EU, where marketing clearance is projected to occur during ;rst-half 2018.
Yescarta is the ;rst product to reach the U.S.
market as a treatment for refractory aggressive
non-Hodgkin lymphoma, which includes DLBCL,
TFL and PMBCL. The FDA and EMA submissions
come after positive results from Kite’s ZUMA-1 pivotal study with axi-cel in patients with chemore-fractory aggressive non-Hodgkin lymphoma.
“Engineered cell therapies like Yescarta rep-
resent the potential for a changing treatment
paradigm for cancer patients,” commented David
Chang, M.D., Ph.D., Worldwide Head of Research
and Development and Chief Medical O;cer at
Kite. “Together, Gilead and Kite will accelerate
studies of CAR T therapy in multiple blood can-
cers and advance other cell therapy approaches
for solid tumors, with the goal of helping patients
with diverse cancers bene;t from this new era of
personalized cancer therapy.”
Physicians say Kite’s promising new technology
for harnessing the body’s immune system to ;ght
cancer could save patients with the most serious
types of cancer. Kite additionally has other prod-
ucts in its pipeline based on similar technology, in-
cluding experimental medicines for multiple my-
eloma, mantle cell lymphoma and solid tumors.
Additional Kite drug candidates in clinical trials
in both hematologic cancers and solid tumors
include KITE-585, a CAR T therapy candidate that
targets BCMA expressed in multiple myeloma.
“The acquisition of Kite establishes Gilead as a
leader in cellular therapy and provides a founda-
tion from which to drive continued innovation for
people with advanced cancers,” noted John F. Milli-
gan, Ph.D., Gilead’s president and CEO. “The ;eld of
cell therapy has advanced very quickly, to the point
where the science and technology have opened a
clear path toward a potential cure for patients.”
Kite Chairman, President and CEO Arie Bellde-
grun, M.D., said at the time of the acquisition an-
nouncement, “CAR T has the potential to become
one of the most powerful anti-cancer agents for
hematologic cancers. With Gilead’s expertise and
support, we hope to ful;ll that potential by rapidly
accelerating our robust pipeline and next-genera-
tion research and manufacturing technologies for
the bene;t of patients around the world.”
The Kite acquisition has provided Gilead with
a robust product pipeline and technology plat-
form to drive future growth: multiple develop-
ment programs are under way to broaden axi-cel
utilization in earlier lines of therapy in aggressive
NHL and other B-cell malignancies; the company
is advancing additional CAR Ts to treat multiple
myeloma and acute myeloid leukemia; and Gilead
is making progress with TCRs for potential use in
“While Kite won’t transform the big biotech’s
;nancial prospects in the near term, the deal de;-nitely deserves to be called transformative because
of the e;ect it will have on Gilead’s position in the
oncology arena,” commented analysts from The
Motley Fool. “By making this one acquisition, Gilead
will instantly become one of the leaders in the exciting new area of using cell therapy to treat cancer.”
Gilead and Kite announced in December a de-;nitive deal to acquire Cell Design Labs, gaining
new technology platforms that will enhance research and development e;orts in cellular therapy. Gilead will acquire all outstanding shares of Cell
Design Labs for up to $567 million, including an
initial upfront payment of $175 million, and other
payments of up to $322 million.
The transaction builds on Gilead’s acquisition of
its cell therapy subsidiary Kite and has the potential to help the two organizations accelerate the
development of next-generation cellular therapy
candidates. Cell Design Labs has signi;cant expertise in custom cell engineering. The pre-clinical
stage company is developing two propriety technology platforms: the synthetic gene expression
system synNotc that responds to external cues
which, among other applications, can be deployed to engineer CAR T cells that require dual
antigen recognition for activation; and Throttle,
an “on switch” that modulates CAR T activity using
small molecules. The addition of these technologies to existing Kite R&D programs could lead to
the treatment of a wider array of hematological
malignancies and solid tumors, and potentially
o;er improved selectivity and safety of future
treatments. Cell Design Labs is also developing
several preclinical product candidates, including
therapies for prostate cancer and hepatocellular