-- If Approved, Yescarta would be the First
CAR T Therapy for Patients with Relapsed or Refractory Follicular
Lymphoma and Marginal Zone Lymphoma --
Kite, a Gilead Company (Nasdaq: GILD), today announced that it
has submitted a supplemental Biologics License Application (sBLA)
to the U.S. Food and Drug Administration (FDA) for Yescarta®
(axicabtagene ciloleucel) for the treatment of relapsed or
refractory follicular lymphoma and marginal zone lymphoma after two
or more prior lines of systemic therapy. Yescarta was previously
granted Breakthrough Therapy Designation (BTD) by the FDA for these
indications. If approved, Yescarta would become the first chimeric
antigen receptor (CAR) T cell therapy approved for the treatment of
relapsed or refractory indolent non-Hodgkin lymphoma (NHL).
The sBLA submission is supported by data from the primary
analysis of the Phase 2 ZUMA-5 trial, which is being submitted for
presentation at an upcoming scientific congress. Findings from an
interim analysis of ZUMA-5 were recently presented during an oral
session at the 2020 American Society of Clinical Oncology (ASCO)
Annual Meeting.
“People living with indolent NHL often experience a disease that
starts out slowly but becomes more aggressive over time with each
subsequent relapse,” said Ken Takeshita, MD, Kite’s Global Head of
Clinical Development. “The efficacy observed in ZUMA-5 may provide
a potentially transformative treatment option for higher-risk
patients with certain types of indolent NHL. We look forward to
working closely with the FDA to progress this application with the
goal of bringing Yescarta to patients with indolent NHL as soon as
possible.”
Yescarta was the first CAR T cell therapy to be 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,
including diffuse large B-cell lymphoma (DLBCL) not otherwise
specified, primary mediastinal large B-cell lymphoma, and high
grade B-cell lymphoma and DLBCL arising from FL. Yescarta is not
indicated for the treatment of patients with primary central
nervous system lymphoma. The Yescarta U.S. Prescribing Information
has a BOXED WARNING for the risks of cytokine release syndrome
(CRS) and neurologic toxicities, and Yescarta is approved with a
risk evaluation and mitigation strategy (REMS) due to these risks;
see below for Important Safety Information.
Yescarta has not been approved by any regulatory agency for the
treatment of indolent non-Hodgkin lymphoma, including follicular
lymphoma or marginal zone lymphoma. Its safety and efficacy have
not been established in these lymphomas.
About Indolent Non-Hodgkin
Lymphoma
Follicular lymphoma and marginal zone lymphoma are both forms of
indolent non-Hodgkin lymphoma (NHL) in which malignant tumors
slowly grow but can become more aggressive over time.
Follicular lymphoma is the most common form of indolent lymphoma
and the second most common type of lymphoma globally. It accounts
for approximately 22 percent of all lymphomas diagnosed worldwide.
Marginal zone lymphoma is the third most common lymphoma,
accounting for 8 to 12 percent of all B-cell NHLs.
Despite advances in management and substantial improvements in
long-term survival, patients living with follicular lymphoma have
varied outcomes. Currently, there are no standard of care
treatments for relapsed and refractory follicular lymphoma after
two or more lines of therapy, and there are limited options for the
treatment of relapsed or refractory marginal zone lymphoma.
About ZUMA-5
ZUMA-5 is a single-arm, multicenter, open-label Phase 2 study
that aims to enroll up to 160 adult patients (≥18 years old) with
relapsed or refractory indolent NHL of either follicular lymphoma
or marginal zone lymphoma subtypes, who received at least two prior
lines of systemic therapy, including an anti-CD20 monoclonal
antibody combined with an alkylating agent. The objectives of the
study are to evaluate the efficacy and safety of a single infusion
of Yescarta in this patient population. The primary endpoint of the
trial is objective response rate (ORR) as assessed by an
independent review committee. Secondary endpoints include complete
response rate, duration of response, progression-free survival,
overall survival, safety and CAR T cell and cytokines levels. The
study is ongoing.
About Yescarta
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 DLBCL not otherwise specified,
primary mediastinal large B-cell lymphoma, high grade B-cell
lymphoma, and DLBCL arising from follicular lymphoma.
Limitation of Use: Yescarta
is not indicated for the treatment of patients with primary central
nervous system lymphoma.
U.S. Important Safety Information for
Yescarta
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 and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of
patients, with 13% ≥ Grade 3. Among patients who died after
receiving Yescarta, 4 had ongoing CRS at death. The median time to
onset was 2 days (range: 1-12 days) and median duration was 7 days
(range: 2-58 days). Key manifestations 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 Yescarta infusion.
Following infusion, monitor patients for signs and symptoms of CRS
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter. 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 occurred in 87% of patients, 98% of
which occurred within the first 8 weeks with a median time to onset
of 4 days (range: 1-43 days) and a median duration of 17 days.
Grade ≥3 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, as well as fatal and serious cases of cerebral edema have
occurred. Following Yescarta infusion, monitor patients for signs
and symptoms of neurologic toxicities at least daily for 7 days at
the certified healthcare facility, and for 4 weeks thereafter, and
treat promptly.
REMS: Because of the risk of CRS and neurologic
toxicities, Yescarta is available only through a restricted program
called the Yescarta and Tecartus REMS Program which requires that:
Healthcare facilities that dispense and administer Yescarta must be
enrolled and comply with the REMS requirements and must have
on-site, immediate access to a minimum of 2 doses of tocilizumab
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.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS: Allergic reactions, including
serious hypersensitivity reactions or anaphylaxis, may occur with
the infusion of Yescarta.
SERIOUS INFECTIONS: Severe or life-threatening infections
occurred. Infections (all grades) occurred in 38% of patients.
Grade ≥3 infections occurred in 23% of patients; those due to 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 infusion and treat appropriately.
Administer prophylactic anti-microbials according to local
guidelines. Febrile neutropenia was observed in 36% of patients 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. 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. Grade ≥3 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 infusion.
HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur.
Hypogammaglobulinemia occurred in 15% of patients. Monitor
immunoglobulin levels after treatment 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.
SECONDARY MALIGNANCIES may develop. Monitor life-long for
secondary malignancies. In the event that one 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 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 (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.
Please see accompanying full Prescribing Information, including
BOXED WARNING and Medication Guide.
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, Inc. is a research-based biopharmaceutical
company that discovers, develops and commercializes innovative
medicines in areas of unmet medical need. The company strives to
transform and simplify care for people with life-threatening
illnesses around the world. Gilead has operations in more than 35
countries worldwide, with headquarters in Foster City, California.
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com.
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,
including the risk that the FDA may not approve Yescarta for the
treatment of relapsed or refractory indolent NHL in the anticipated
timelines or at all, and any marketing approvals, if granted, may
have significant limitations on its use. There is also the
possibility of unfavorable results from other ongoing and
additional clinical trials involving Yescarta. All statements other
than statements of historical fact are statements that could be
deemed forward-looking statements. These risks, uncertainties and
other factors could cause actual results to differ materially from
those referred to in the forward-looking statements. The reader is
cautioned not to rely on these forward-looking statements. These
and other risks are described in detail in Gilead’s Quarterly
Report on Form 10-Q for the quarter ended June 30, 2020, as filed
with the U.S. Securities and Exchange Commission. All
forward-looking statements are based on information currently
available to Gilead and Kite, and Gilead and Kite assume no
obligation to update any such forward-looking statements.
U.S. Prescribing Information for Yescarta,
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Kite, the Kite logo, Yescarta, Tecartus and
GILEAD are trademarks of Gilead Sciences, Inc. or its related
companies.
For more information on Kite, please visit the
company’s website at www.kitepharma.com or call Gilead Public
Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Follow Kite on social
media on Twitter (@KitePharma) and LinkedIn.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200904005123/en/
Douglas Maffei, PhD, Investors (650) 522-2739
Nathan Kaiser, Media (650) 522-1853
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