-- 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 www.yescartarems.com. 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
transplant.
“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 therapy.”
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 population.
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 www.yescarta.com.
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 www.KiteKonnect.com 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.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME and
NEUROLOGIC TOXICITIES
- 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 REMS.
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 (HLH/MAS).
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
www.YescartaREMS.com 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 infusion.
Hypogammaglobulinemia
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 difficile 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
www.kitepharma.com.
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 www.yescarta.com.
For more information on Gilead Sciences,
please visit the company’s website at www.gilead.com, follow
Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
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Gilead SciencesInvestorsSung Lee, 650-524-7792orMediaAmy Flood,
650-522-5643
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