Market Overview

Kite's Yescarta™ (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy


-- Manufacturing Success Rate of 99 Percent in ZUMA-1 Pivotal
Trial with a Median 17 Day Turnaround Time --

Kite, a Gilead Company, (NASDAQ:GILD) today announced that the U.S.
Food and Drug Administration (FDA) has granted regular approval to
Yescarta™ (axicabtagene ciloleucel), the first chimeric antigen receptor
T cell (CAR T) therapy for the treatment of adult patients with relapsed
or refractory large B-cell lymphoma after two or more lines of systemic
therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise
specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade
B-cell lymphoma, and DLBCL arising from follicular lymphoma (transformed
follicular lymphoma, or TFL). Yescarta is not indicated for the
treatment of patients with primary central nervous system lymphoma.

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CAR T therapy is a breakthrough in hematologic cancer treatment in which
a patient's own T cells are engineered to seek and destroy cancer cells.
CAR T therapy is manufactured specifically for each individual patient.

"The FDA approval of Yescarta is a landmark for patients with relapsed
or refractory large B-cell lymphoma. This approval would not have been
possible without the courageous commitment of patients and clinicians,
as well as the ongoing dedication of Kite's employees," said Arie
Belldegrun, MD, FACS, Founder of Kite. "We must also recognize the FDA
for their ability to embrace and support transformational new
technologies that treat life-threatening illnesses. We believe this is
only the beginning for CAR T therapies."

"Today is an important day for patients with relapsed or refractory
large B-cell lymphoma who have run out of options and have been waiting
for new treatments that may help them in their fight against cancer,"
said John Milligan, PhD, President and Chief Executive Officer of Gilead
Sciences. "With the combined innovation, talent and drive of the Kite
and Gilead teams, we will rapidly advance cell therapy research and aim
to bring new options to patients with many other types of cancer."

Yescarta has a Boxed Warning in its product label regarding the risks of
cytokine release syndrome (CRS) and neurologic toxicities. A Risk
Evaluation and Mitigation Strategy (REMS) has been approved by the FDA
for Yescarta. The REMS program will inform and educate healthcare
professionals about the risks associated with Yescarta therapy. Training
and certification on the REMS program will be an integral part of the
final authorization for centers offering Yescarta. Additional
information about the REMS program can be found at
Please see below for Important Safety Information.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive
non-Hodgkin lymphoma (NHL), accounting for three out of every five
cases. In the United States each year, there are approximately 7,500
patients with refractory DLBCL who are eligible for CAR T therapy.
Historically, when treated with the current standard of care, patients
with refractory large B-cell lymphoma had a median overall survival of
approximately six months, with only seven percent attaining a complete
response. Currently, patients with large B-cell lymphoma in second or
later lines of therapy have poor outcomes and greater unmet need, since
nearly half of them either do not respond or relapse shortly after

"With CAR T therapy, we are reengineering a patient's own immune system
to detect and kill cancer cells, and the results have been impressive,"
said Frederick L. Locke, MD, ZUMA-1 Co-Lead Investigator and Vice Chair
of the Department of Blood and Marrow Transplant and Cellular
Immunotherapy at Moffitt Cancer Center in Tampa, Florida. "Many of the
patients that received CAR T therapy had already relapsed several times
with traditional treatments such as chemotherapy or hematopoietic stem
cell transplant. Now, thanks to this new therapy many patients are in
remission for months."

"This therapy is a new option for patients with relapsed or refractory
large B-cell lymphoma who have run out of treatment options and face a
dire prognosis," said Louis J. DeGennaro, PhD, President and Chief
Executive Officer of The Leukemia & Lymphoma Society (LLS). "Early on,
LLS recognized the potential of CAR T therapy and we are proud to be
part of making this historic approval possible."

"Engineered cell therapies like Yescarta represent the potential for a
changing treatment paradigm for cancer patients," said David Chang, MD,
PhD, Worldwide Head of Research and Development and Chief Medical
Officer at Kite. "Together, Gilead and Kite will accelerate studies of
CAR T therapy in multiple blood cancers and advance other cell therapy
approaches for solid tumors, with the goal of helping patients with
diverse cancers benefit from this new era of personalized cancer

Yescarta will be manufactured in Kite's state-of-the-art commercial
manufacturing facility in El Segundo, California. In the ZUMA-1 pivotal
trial, Kite demonstrated a 99 percent manufacturing success rate with a
median manufacturing turnaround time of 17 days, which is important to
patients given the potential for rapid disease progression in this

In 2017, Kite established a multi-disciplinary field team focused on
providing education and logistics training for centers. Upon Yescarta's
approval, this team will provide final site certification to 16 centers,
enabling them to make Yescarta available to appropriate patients. This
support is designed to assure the safe and effective use of Yescarta for
patients and physicians. Kite is actively working to train more than 30
additional centers with an eventual target of 70 to 90 centers across
the United States. The latest information on Yescarta authorized centers
is available at

In support of Yescarta therapy, Kite has developed Kite Konnect™, a
program enabled by an integrated technology platform that focuses on
providing information and assistance throughout the Yescarta therapy
process, including courier tracking for shipments and manufacturing
status updates. Kite Konnect also will provide information related to
insurance benefits and third-party resources available for travel
support. Healthcare providers and patients can reach Kite Konnect at
or 1-844-454-KITE (1-844-454-5483).

The list price of Yescarta in the United States is $373,000.

Yescarta has been granted Priority Medicines (PRIME) regulatory support
for DLBCL in the European Union. A Marketing Authorization Application
(MAA) for axicabtagene ciloleucel is currently under review with the
European Medicines Agency (EMA) and potential approval is expected in
the first half of 2018.

Yescarta (axicabtagene ciloleucel) Pivotal
Trial Results

The approval of Yescarta is supported by data from the ZUMA-1 pivotal
trial. In this study, 72 percent of patients treated with a single
infusion of Yescarta (n=101) responded to therapy (overall response
rate) including 51 percent of patients who had no detectable cancer
remaining (complete remission; 95% CI: 41, 62). At a median follow-up of
7.9 months, patients who had achieved a complete remission had not
reached the estimated median duration of response (95% CI: 8.1 months,
not estimable [NE]).

In the study, 13 percent of patients experienced grade 3 or higher
cytokine release syndrome (CRS) and 31 percent experienced neurologic
toxicities. The most common (≥ 10%) Grade 3 or higher reactions include
febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen
unspecified, hypotension, hypoxia and lung infections. Serious adverse
reactions occurred in 52% of patients and included CRS, neurologic
toxicity, prolonged cytopenias (including neutropenia, thrombocytopenia
and anemia), and serious infections. Fatal cases of CRS and neurologic
toxicity occurred. FDA approved Yescarta with a Risk Evaluation and
Mitigation Strategy.

Yescarta Indication

Yescarta is a CD19-directed genetically modified autologous T cell
immunotherapy indicated for the treatment of adult patients with
relapsed or refractory large B-cell lymphoma after two or more lines of
systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not
otherwise specified, primary mediastinal large B-cell lymphoma,
high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Yescarta is not indicated for the treatment of patients with primary
central nervous system lymphoma.



  • Cytokine Release Syndrome (CRS), including fatal or
    life-threatening reactions, occurred in patients receiving Yescarta.
    Do not administer Yescarta to patients with active infection or
    inflammatory disorders. Treat severe or life-threatening CRS with
    tocilizumab or tocilizumab and corticosteroids.
  • Neurologic toxicities, including fatal or life-threatening
    reactions, occurred in patients receiving Yescarta, including
    concurrently with CRS or after CRS resolution. Monitor for neurologic
    toxicities after treatment with Yescarta. Provide supportive care
    and/or corticosteroids as needed.
  • Yescarta is available only through a restricted program under a
    Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta

Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following
treatment with Yescarta. In Study 1, CRS occurred in 94% (101/108) of
patients receiving Yescarta, including ≥ Grade 3 (Lee grading system)
CRS in 13% (14/108) of patients. Among patients who died after receiving
Yescarta, four had ongoing CRS events at the time of death. The median
time to onset was 2 days (range: 1 to 12 days) and the median duration
of CRS was 7 days (range: 2 to 58 days). Key manifestations of CRS
include fever (78%), hypotension (41%), tachycardia (28%), hypoxia
(22%), and chills (20%). Serious events that may be associated with CRS
include cardiac arrhythmias (including atrial fibrillation and
ventricular tachycardia), cardiac arrest, cardiac failure, renal
insufficiency, capillary leak syndrome, hypotension, hypoxia, and
hemophagocytic lymphohistiocytosis/macrophage activation syndrome

Ensure that 2 doses of tocilizumab are available prior to infusion of
Yescarta. Monitor patients at least daily for 7 days at the certified
healthcare facility following infusion for signs and symptoms of CRS.
Monitor patients for signs or symptoms of CRS for 4 weeks after
infusion. Counsel patients to seek immediate medical attention should
signs or symptoms of CRS occur at any time. At the first sign of CRS,
institute treatment with supportive care, tocilizumab or tocilizumab and
corticosteroids as indicated.

Neurologic Toxicities

Neurologic toxicities, that were fatal or life-threatening, occurred
following treatment with Yescarta. Neurologic toxicities occurred in 87%
of patients. Ninety-eight percent of all neurologic toxicities occurred
within the first 8 weeks of Yescarta infusion, with a median time to
onset of 4 days (range: 1 to 43 days). The median duration of neurologic
toxicities was 17 days. Grade 3 or higher neurologic toxicities occurred
in 31% of patients.

The most common neurologic toxicities included encephalopathy (57%),
headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium
(17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting
up to 173 days was noted. Serious events including leukoencephalopathy
and seizures occurred with Yescarta. Fatal and serious cases of cerebral
edema have occurred in patients treated with Yescarta.

Monitor patients at least daily for 7 days at the certified healthcare
facility following infusion for signs and symptoms of neurologic
toxicities. Monitor patients for signs or symptoms of neurologic
toxicities for 4 weeks after infusion and treat promptly.

Yescarta REMS

Because of the risk of CRS and neurologic toxicities, Yescarta is
available only through a restricted program under a Risk Evaluation and
Mitigation Strategy (REMS) called the Yescarta REMS. The required
components of the Yescarta REMS are:

  • Healthcare facilities that dispense and administer Yescarta must be
    enrolled and comply with the REMS requirements. Certified healthcare
    facilities must have on-site, immediate access to tocilizumab, and
    ensure that a minimum of two doses of tocilizumab are available for
    each patient for infusion within 2 hours after Yescarta infusion, if
    needed for treatment of CRS.
  • Certified healthcare facilities must ensure that healthcare providers
    who prescribe, dispense or administer Yescarta are trained about the
    management of CRS and neurologic toxicities.

Further information is available at
or 1-844-454-KITE (5483).

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of Yescarta. Serious
hypersensitivity reactions including anaphylaxis, may be due to dimethyl
sulfoxide (DMSO) or residual gentamicin in Yescarta.

Serious Infections

Severe or life-threatening infections occurred in patients after
Yescarta infusion. In Study 1, infections (all grades) occurred in 38%
of patients. Grade 3 or higher infections occurred in 23% of patients.
Grade 3 or higher infections with an unspecified pathogen occurred in
16% of patients, bacterial infections in 9%, and viral infections in 4%.
Yescarta should not be administered to patients with clinically
significant active systemic infections. Monitor patients for signs and
symptoms of infection before and after Yescarta infusion and treat
appropriately. Administer prophylactic anti-microbials according to
local guidelines.

Febrile neutropenia was observed in 36% of patients after Yescarta
infusion and may be concurrent with CRS. In the event of febrile
neutropenia, evaluate for infection and manage with broad spectrum
antibiotics, fluids and other supportive care as medically indicated.

Viral Reactivation

Hepatitis B virus (HBV) reactivation, in some cases resulting in
fulminant hepatitis, hepatic failure and death, can occur in patients
treated with drugs directed against B cells. Perform screening for HBV,
HCV, and HIV in accordance with clinical guidelines before collection of
cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias for several weeks following
lymphodepleting chemotherapy and Yescarta infusion. In Study 1, Grade 3
or higher cytopenias not resolved by Day 30 following Yescarta infusion
occurred in (28%) of patients and included thrombocytopenia (18%),
neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta


B-cell aplasia and hypogammaglobulinemia can occur in patients receiving
treatment with Yescarta. In Study 1, hypogammaglobulinemia occurred in
15% of patients. Monitor immunoglobulin levels after treatment with
Yescarta and manage using infection precautions, antibiotic prophylaxis
and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following
Yescarta treatment has not been studied. Vaccination with live virus
vaccines is not recommended for at least 6 weeks prior to the start of
lymphodepleting chemotherapy, during Yescarta treatment, and until
immune recovery following treatment with Yescarta.

Secondary Malignancies

Patients treated with YESCARTA may develop secondary malignancies.
Monitor life-long for secondary malignancies. In the event that a
secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to
obtain instructions on patient samples to collect for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental
status or seizures, patients receiving Yescarta are at risk for altered
or decreased consciousness or coordination in the 8 weeks following
Yescarta infusion. Advise patients to refrain from driving and engaging
in hazardous occupations or activities, such as operating heavy or
potentially dangerous machinery, during this initial period.

Adverse Reactions

The most common adverse reactions (incidence ≥ 20%) include CRS, fever,
hypotension, encephalopathy, tachycardia, fatigue, headache, decreased
appetite, chills, diarrhea, febrile neutropenia, infections-pathogen
unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness,
constipation, and cardiac arrhythmias. Serious adverse reactions
occurred in 52% of patients. The most common serious adverse reactions
(> 2%) include encephalopathy, fever, lung infection, febrile
neutropenia, cardiac arrhythmia, cardiac failure, urinary tract
infection, renal insufficiency, aphasia, cardiac arrest, Clostridium
infection, delirium, hypotension, and hypoxia.

The most common (≥ 10%) Grade 3 or higher reactions include febrile
neutropenia, fever, CRS, encephalopathy, infections-pathogen
unspecified, hypotension, hypoxia and lung infections.

About Kite

Kite, a Gilead Company, is a biopharmaceutical company based in Santa
Monica, California. Kite is engaged in the development of innovative
cancer immunotherapies. The company is focused on chimeric antigen
receptor and T cell receptor engineered cell therapies. For more
information on Kite, please visit

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The company's mission is to advance the care of patients suffering
from life-threatening diseases. Gilead has operations in more than 30
countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors. All statements other
than statements of historical fact are statements that could be deemed
forward-looking statements, including all statements regarding the
intent, belief or current expectation of the companies' and members of
their senior management team. Forward-looking statements include,
without limitation, the risk that physicians may not see the benefits of
prescribing Yescarta for the diseases for which it is approved; the
ability of Kite to continue to manufacture Yescarta at the success rates
experienced during clinical trials; the possibility of unfavorable
results from additional clinical trials involving Yescarta; and the risk
that other regulatory agencies may not approve Yescarta in the currently
anticipated timelines or at all, and that any marketing approvals may
have significant limitations on its use. Investors are cautioned that
any such forward-looking statements are not guarantees of future
performance and involve risks and uncertainties and are cautioned not to
place undue reliance on these forward-looking statements. Actual results
may differ materially from those currently anticipated due to a number
of risks and uncertainties. Risks and uncertainties that could cause the
actual results to differ from expectations contemplated by
forward-looking statements include risks and uncertainties detailed from
time to time in the companies' periodic reports filed with the
Securities and Exchange Commission, including current reports on Form
8-K, quarterly reports on Form 10-Q and annual reports on Form 10-K. All
forward-looking statements are based on information currently available
to Gilead and Kite, and Gilead and Kite assume no obligation and
disclaim any intent to update any such forward-looking statements.

US Prescribing Information for Yescarta, including BOXED WARNING and
Medication Guide, is available at

For more information on Gilead Sciences, please visit the company's
website at,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.

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