-- 92 Percent of Patients with Relapsed or
Refractory iNHL Achieved a Response to Yescarta, Including 76
Percent with a Complete Response --
-- Primary Analysis Supports Supplemental
Biologics License Application (sBLA) for Yescarta Currently Under
Priority Review by the U.S. Food & Drug Administration (FDA)
--
Kite, a Gilead Company (Nasdaq: GILD), today announced results
from the primary analysis of ZUMA-5, a global, multicenter,
single-arm, open-label Phase 2 study evaluating Yescarta®
(axicabtagene ciloleucel) in adult patients with relapsed or
refractory indolent non-Hodgkin lymphoma (iNHL) after at least two
prior lines of therapy. After a single infusion of Yescarta, 92
percent of iNHL patients (n=104 evaluable for efficacy) responded,
including 76 percent of patients achieving a complete response (CR)
at a median follow-up of 17.5 months. The data are being presented
in an oral session during the 62nd American Society of Hematology
(ASH) Annual Meeting and Exposition (Abstract #700). The
presentation is also being considered for Best of ASH and has been
selected for inclusion in the ASH Annual Meeting Press Program.
Based on these data, the U.S. Food and Drug Administration (FDA)
has accepted the supplemental Biologics License Application (sBLA)
and granted Priority Review designation for Yescarta for the
treatment of relapsed or refractory follicular lymphoma (FL) and
marginal zone lymphoma (MZL) after two or more prior lines of
systemic therapy, with a target action date under the Prescription
Drug User Fee Act (PDUFA) of March 5, 2021. Yescarta has previously
been granted a Breakthrough Therapy Designation (BTD) by the FDA
for these indications. If approved, Yescarta would become the first
chimeric antigen receptor (CAR) T therapy approved for the
treatment of relapsed or refractory indolent NHLs.
“It is encouraging to see this level of response to CAR T-cell
therapy in a heavily pretreated and multiply relapsed patient
population, in whom response duration to other available therapies
is expected to be short,” 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. “Our goal with treatment is to prolong overall survival,
and the impressive durability following a one-time treatment of
axicabtagene ciloleucel is incredibly promising for
relapsed/refractory patients, who are often at a higher risk for
early progression.”
Ninety-four percent of patients with relapsed or refractory FL
(n=84) responded to Yescarta, including 80 percent of patients
achieving a CR and 64 percent of patients in an ongoing response at
a median follow-up of 17.5 months. Of patients with relapsed or
refractory MZL (n=20), 85 percent responded to Yescarta, with 60
percent achieving a CR. Median duration of response (DOR),
progression-free survival (PFS) and overall survival (OS) were not
reached.
In the safety analysis (n=146), Grade 3 or higher cytokine
release syndrome (CRS) and neurologic events (NEs) occurred in 7
percent and 19 percent of patients, respectively. Lower incidence
of Grade 3 or higher NEs was observed in patients with FL (15
percent) compared to MZL (41 percent), and CRS rates were
comparable between the two groups. There were three Grade 5 adverse
events, including one patient with multisystem organ failure in the
context of CRS related to treatment with Yescarta, one with aortic
dissection unrelated to Yescarta treatment, and one with
coccidioidomycosis infection unrelated to Yescarta treatment.
“As we continue to advance Kite’s cell therapy franchise, this
analysis further demonstrates the practice-changing potential of
Yescarta in additional hematologic malignancies,” said Ken
Takeshita, MD, Kite’s Global Head of Clinical Development. “We’re
excited about the potential role of Yescarta in indolent NHL and
look forward to continuing to work with the FDA to bring it to
these patients as soon as possible.”
Kite has presented four-year survival data for Yescarta in the
ZUMA-1 study of patients with refractory large B-cell lymphoma.
Based on these data and other data presented at ASH, Kite believes
that Yescarta could bring the hope of survival to patients with a
number of other hematological malignancies.
Yescarta has not been approved by any regulatory agency for the
treatment of indolent NHL, including FL or MZL. Its safety and
efficacy have not been established in these lymphomas.
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 (PMBCL), 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 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 Non-Hodgkin
Lymphoma
Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are
both forms of indolent non-Hodgkin lymphoma (NHL) 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. MZL
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 FL have varied outcomes.
Currently, there are limited options for the treatment of relapsed
or refractory FL and MZL after two or more lines of therapy.
About ZUMA-5
ZUMA-5 is a single-arm, multicenter, open-label Phase 2 study
that aims to enroll patients (≥18 years old) with relapsed or
refractory iNHL of either follicular lymphoma (FL) or marginal zone
lymphoma (MZL) 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 per the 2014 Lugano Classification.
Secondary endpoints include CR rate, DOR, PFS, OS, safety and CAR T
cell and cytokines levels. The study is ongoing.
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 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 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 September 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/20201205005008/en/
Douglas Maffei, PhD, Investors (650) 522-2739
Nathan Kaiser, Media (650) 522-1853
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