-- Yescarta is the First CAR T-Cell Therapy
Approved for Indolent Follicular Lymphoma; Approval Marks the Third
Indication for a Kite Cell Therapy --
-- 91 Percent of Patients Responded to
Yescarta, and Median Duration of Response Was Not Yet Reached in
the ZUMA-5 Trial --
Kite, a Gilead Company (Nasdaq: GILD), today announced that the
U.S. Food and Drug Administration (FDA) has granted accelerated
approval to Yescarta® (axicabtagene ciloleucel) for the
treatment of adult patients with relapsed or refractory follicular
lymphoma (FL) after two or more lines of systemic therapy. The
approval makes Yescarta the first chimeric antigen receptor (CAR)
T-cell therapy approved for patients with indolent follicular
lymphoma, follows FDA Breakthrough Therapy Designation and a
priority review, and marks the third approved indication for a Kite
cell therapy.
The approval is based on results from ZUMA-5, a single-arm,
open-label study in which 91 percent of patients with relapsed or
refractory FL (n=81) responded to Yescarta, including an estimated
74 percent of patients in a continued remission at 18 months
(Kaplan-Meier estimate). Among all FL patients, median duration of
response was not reached at a median follow-up of 14.5 months. In
the safety analysis set (n=146), Grade 3 or higher cytokine release
syndrome (CRS) and neurologic toxicities occurred in 8 percent and
21 percent of patients, respectively.
“Once a follicular lymphoma patient’s disease relapses, the
duration of response to care shortens with each round of therapy,”
said Caron A. Jacobson, MD, MMSc, Medical Director, Immune Effector
Cell Therapy Program, Dana-Farber Cancer Institute and Assistant
Professor of Medicine, Harvard Medical School. “Additionally, for
follicular patients in the third line of therapy, the five-year
survival rate is only 20 percent, highlighting the urgent need for
treatments that offer a real chance for durable remission.
Impressively, 91 percent of follicular lymphoma patients in the
ZUMA-5 study responded to a single infusion of axicabtagene
ciloleucel, including an estimated 74 percent of patients in a
continued remission at 18 months, giving these patients much-needed
hope and oncologists an important addition to the treatment
armamentarium.”
“As we look to bring the hope of survival to more patients in
need, today’s FDA decision represents a real step forward in our
commitment in hematologic malignancies,” said Christi Shaw, Chief
Executive Officer of Kite. “Advancing CAR T therapies for patients
across lymphomas remains a cornerstone of our cell therapy
development program, and we are excited about the potential of
Yescarta for patients with indolent follicular lymphoma.”
Patients whose healthcare professionals have prescribed Yescarta
therapy can work with Kite Konnect®, an integrated technology
platform that provides information and assistance throughout the
therapy process for Kite’s commercialized CAR T therapies,
including courier tracking for shipments and manufacturing status
updates. More information is available at www.kitekonnect.com.
“This is an important new treatment option for people with
third-line relapsed or refractory follicular lymphoma,” said Lee
Greenberger, PhD, Chief Scientific Officer of The Leukemia &
Lymphoma Society (LLS). “LLS has supported CAR T development from
the beginning, and on behalf of blood cancer patients, we thank
Kite and Gilead for their work in bringing this remarkably
innovative treatment to more patients.”
The Yescarta U.S. Prescribing Information has a BOXED WARNING
for the risks of 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.
About Indolent Follicular
Lymphoma
Follicular lymphoma (FL) is a form of indolent non-Hodgkin
lymphoma (iNHL) in which malignant tumors slowly grow but can
become more aggressive over time. FL 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. Currently, there are limited options for the
treatment of relapsed or refractory indolent FL after two or more
lines of therapy.
ZUMA-5 Trial Results
ZUMA-5 is an ongoing, single-arm, open-label, multicenter trial
evaluating 146 patients (≥18 years old) with relapsed or refractory
iNHL, who received at least two prior lines of systemic therapy,
including the combination of an anti-CD20 monoclonal antibody and
an alkylating agent. Efficacy was established on the basis of
objective response rate (ORR) and duration of response (DoR) as
assessed by an independent review committee per the 2014 Lugano
Classification.
In the study, 91 percent of all FL patients (n=81 evaluable for
efficacy analysis) responded to a single infusion of Yescarta,
including 60 percent of patients who achieved a complete remission.
Thirteen of the 25 patients who achieved a partial remission met
imaging criteria for a complete remission without confirmation by
negative bone marrow biopsy after treatment. Median DoR has not yet
been reached.
Among the 146 patients evaluable for safety, Grade 3 or higher
CRS and neurologic toxicities were observed in 8 percent and 21
percent of patients, respectively. The median time to onset of CRS
and neurologic toxicities were four days (range: 1 to 20 days) and
six days (range 1 to 79 days), respectively. The most common (≥10
percent) Grade 3 or higher adverse reactions included febrile
neutropenia, encephalopathy, and infections with pathogen
unspecified.
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
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. Limitations of Use: Yescarta is not indicated for
the treatment of patients with primary central nervous system
lymphoma.
- Adult patients with relapsed or refractory follicular lymphoma
(FL) after two or more lines of systemic therapy. This indication
is approved under accelerated approval based on response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trial(s).
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), including fatal or
life-threatening reactions, occurred. CRS occurred in 88% (224/254)
of all patients with non-Hodgkin lymphoma (NHL), including Grade ≥3
in 10%. CRS occurred in 94% (101/108) of patients with large B-cell
lymphoma (LBCL), including Grade ≥3 in 13%. Among patients with
LBCL who died after receiving Yescarta, 4 had ongoing CRS events at
the time of death. The median time to onset of CRS was 2 days
(range: 1-12 days) and the median duration was 7 days (range: 2-58
days) for patients with LBCL. CRS occurred in 84% (123/146) of
patients with indolent non-Hodgkin lymphoma (iNHL), including Grade
≥3 in 8% (11/146). Among patients with iNHL who died after
receiving Yescarta, 1 patient had ongoing CRS events at the time of
death. The median time to onset of CRS was 4 days (range: 1-20
days) and median duration was 6 days (range: 1-27 days) for
patients with iNHL. Key manifestations of CRS (≥10%) in all
patients combined included fever (80%), hypotension (38%),
tachycardia (29%), hypoxia (21%), chills (21%), and headache (13%).
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, multi-organ failure,
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 that were fatal or life-threatening
occurred. Neurologic toxicities occurred in 81% (206/254) of all
patients with NHL receiving Yescarta, including Grade ≥3 in 26%.
Neurologic toxicities occurred in 87% (94/108) of patients with
LBCL, including Grade ≥3 in 31%. The median time to onset was 4
days (range: 1-43 days) and the median duration was 17 days for
patients with LBCL. Neurologic toxicities occurred in 77% (112/146)
of patients with iNHL, including Grade ≥3 in 21%. The median time
to onset was 6 days (range: 1-79 days) and the median duration was
16 days for patients with iNHL. 98% of all neurologic toxicities in
patients with LBCL and 99% of all neurologic toxicities in patients
with iNHL occurred within the first 8 weeks of Yescarta infusion.
Neurologic toxicities occurred within the first 7 days of infusion
for 89% of patients with LBCL and 74% of patients with iNHL. The
most common neurologic toxicities (≥10%) in all patients combined
included encephalopathy (53%), headache (45%), tremor (31%),
dizziness (20%), delirium (16%), aphasia (15%), and insomnia (11%).
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 47% (119/254) of all
patients with NHL. Grade ≥3 infections occurred in 19% of patients,
Grade ≥3 infections with an unspecified pathogen occurred in 15%,
bacterial infections in 5%, viral infections in 2%, and fungal
infections in 1%. 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 40% of all patients with NHL 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. In immunosuppressed
patients, including those who have received Yescarta,
life-threatening and fatal opportunistic infections including
disseminated fungal infections (e.g., candida sepsis and
aspergillus infections) and viral reactivation (e.g., human herpes
virus-6 [HHV-6] encephalitis and JC virus progressive multifocal
leukoencephalopathy [PML]) have been reported. The possibility of
HHV-6 encephalitis and PML should be considered in immunosuppressed
patients with neurologic events and appropriate diagnostic
evaluations should be performed. 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 30% of all patients with NHL and
included neutropenia (22%), thrombocytopenia (13%), and anemia
(5%). Monitor blood counts after infusion.
HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur.
Hypogammaglobulinemia occurred in 17% of all patients with NHL.
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 adverse reactions
(incidence ≥20%) in patients with LBCL included CRS, fever,
hypotension, encephalopathy, tachycardia, fatigue, headache,
decreased appetite, chills, diarrhea, febrile neutropenia,
infections with pathogen unspecified, nausea, hypoxia, tremor,
cough, vomiting, dizziness, constipation, and cardiac arrhythmias.
The most common non-laboratory adverse reactions (incidence ≥20%)
in patients with iNHL included fever, CRS, hypotension,
encephalopathy, fatigue, headache, infections with pathogen
unspecified, tachycardia, febrile neutropenia, musculoskeletal
pain, nausea, tremor, chills, diarrhea, constipation, decreased
appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide.
About Kite
Kite, a Gilead Company, is a biopharmaceutical company based in
Santa Monica, California, with commercial manufacturing operations
in North America and Europe. 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 biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis and cancer. Gilead operates 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
Statements
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 physicians and patients may not see the
potential benefits of Yescarta therapy and the possibility of
unfavorable results from other ongoing and additional clinical
studies involving Yescarta for the treatment of relapsed or
refractory follicular lymphoma or other potential indications. 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 Annual Report on Form 10-K for the year ended
December 31, 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, Kite
Konnect 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/20210305005624/en/
Jacquie Ross, Investors (408) 656-8793
Nathan Kaiser, Media (650) 522-1853
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