-- ZUMA-1 Data Suggest Patient Response to
Yescarta® (axicabtagene ciloleucel) at Three Months
May be Predictive of Longer-Term Response in Refractory B-cell
Lymphoma --
-- ZUMA-3 Analysis Suggests High Complete
Response Rates with KTE-C19 in Adult Patients with Relapsed or
Refractory Acute Lymphoblastic Leukemia (ALL) Regardless of Prior
Blinatumomab Treatment --
Kite, a Gilead Company (Nasdaq: GILD), today announced new
analyses from the ZUMA chimeric antigen receptor T (CAR T) cell
therapy development program that are being presented at the 2018
American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago. The results include analyses of the ZUMA-1 study of
Yescarta® (axicabtagene ciloleucel) in adult patients with
refractory large B-cell lymphoma showing that response status may
predict rates of progression-free survival (PFS) (Abstract #3003)
and that treatment responses were consistent across prior lines of
therapy (Abstract #3039). Additionally, an analysis of the ZUMA-3
study evaluating investigational KTE-C19 for the treatment of adult
patients with relapsed or refractory acute lymphoblastic leukemia
(ALL) showed that patients experienced manageable safety and
encouraging efficacy irrespective of prior blinatumomab use
(Abstract #7006).
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“With the U.S. approval of Yescarta last year, we aim to
transform the treatment of patients with refractory large B-cell
lymphoma,” said Alessandro Riva, MD, Gilead’s Executive Vice
President, Oncology Therapeutics & Head, Cell Therapy. “We are
also committed to studying Yescarta and other CD19-directed CAR T
therapies for people with other relapsed or refractory blood
cancers. Based on the strength of the ZUMA-1 data, we are now
evaluating the potential of Yescarta in the second-line treatment
setting in a Phase 3 study, ZUMA-7, and we continue to evaluate
KTE-C19 in Phase 1/2 studies in ALL and other hematologic
cancers.”
Yescarta was the first CAR T cell therapy to be approved by the
U.S. Food and Drug Administration (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, 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.
Yescarta has a Boxed Warning in its product label and an
associated Risk Evaluation and Mitigation Strategy (REMS) regarding
the risks of CRS and neurologic toxicities. Please see below for
Important Safety Information.
A Marketing Authorization Application (MAA) for axicabtagene
ciloleucel is currently under review with the European Medicines
Agency (EMA).
Ongoing Responses, Response by Prior Lines of Therapy in
ZUMA-1 (Abstracts #3003 and #3039)
Long-term ZUMA-1 follow-up data have shown an overall response
rate (ORR) of 83 percent (n=84/101), including 58 percent
(n=59/101) of patients with a complete response at a median
follow-up of 15.1 months. In this long-term follow-up, Grade 3 or
higher cytokine release syndrome (CRS) and neurologic events were
seen in 12 percent and 29 percent of patients, respectively.
A new analysis of ZUMA-1 suggests that response status three
months after infusion of Yescarta may be predictive of longer-term
disease control. Of the 42 patients with complete response and nine
with partial response at three months, the 12-month PFS rates were
79 percent and 78 percent, respectively. This abstract has also
been selected for inclusion in the 2018 Best of ASCO® program.
“We are encouraged by the strong long-term complete response
rates in ZUMA-1, which represents a patient population that
previously had few if any remaining treatment options,” 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.
“Importantly, this new study analysis indicates that response
status at three months is potentially predictive of prolonged
PFS.”
An additional ZUMA-1 analysis evaluated outcomes based on prior
therapy the patients had received. The results indicate long-term
clinical benefit for patients with refractory large B cell
lymphoma, irrespective of the number of prior lines of therapy.
Rates of Response with Prior Blinatumomab Treatment in ZUMA-3
(Abstract #7006)
Phase 1 data for KTE-C19, an investigational CD19 CAR T cell
therapy, presented at the 2017 Annual Meeting of the American
Society of Hematology (ASH) demonstrated high rates of complete
response in adult patients with relapsed or refractory acute
lymphoblastic leukemia (ALL). A new analysis of data from the
ZUMA-3 study shows patients responded to KTE-C19 regardless of
prior treatment with blinatumomab, an FDA-approved treatment for
relapsed or refractory ALL. After eight or more weeks of follow-up,
63 percent (n=5/8) of patients with prior blinatumomab treatment
and 80 percent (n=8/10) of patients without prior blinatumomab
treatment had achieved a complete response or complete response
with incomplete hematological recovery. Overall, 94 percent
(n=17/18) of patients had minimal residual disease (MRD)-negative
remission. KTE-C19 was also manufactured successfully in both
groups, with similar product characteristics in terms of CD4/CD8
ratio and other measures.
“As a CD19/CD3 bispecific T cell antibody, the possible impact
of prior blinatumomab use on the efficacy of KTE-C19 – a
CD19-directed CAR T therapy – was an important question for
exploration,” said Bijal Shah, MD, ZUMA-3 investigator and medical
oncologist, Moffitt Cancer Center. “We observed that prior
blinatumomab use did not affect the manufacturing of efficacious
product, and that high response rates were seen regardless of
previous treatment with blinatumomab.”
Grade 3 or higher CRS was seen in 27 percent of patients with
prior blinatumomab and in 17 percent of patients without prior
blinatumomab. Grade 3 or higher neurologic events were seen in 36
percent of patients with prior blinatumomab and 67 percent of
patients without prior blinatumomab. A greater number of subjects
in the blinatumomab-naïve group received the higher 1 × 106
cells/kg dose.
KTE-C19 for ALL is investigational and has not been proven safe
or efficacious.
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®
REMS.
CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of
patients, including 13% with ≥ 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 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 occurred in
87% of patients. Ninety-eight percent of all neurologic toxicities
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
or higher 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 2
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.
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. Infections (all grades) occurred in 38% of patients, and
in 23% with ≥ Grade 3. 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 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 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. 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: Patients 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 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.
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 Kite’s ability to complete the Phase 3 study of Yescarta
for the treatment of relapsed or refractory large B-cell lymphoma
(ZUMA-7) and the Phase 1/2 studies of KTE-C19 for the treatment of
acute lymphoblastic leukemia and other hematologic cancers in the
currently anticipated timelines, or at all. In addition, there is
the possibility of unfavorable results from additional clinical
trials involving Yescarta and KTE-C19. Further, Kite may be unable
to obtain regulatory approval for axicabtagene ciloleucel from the
European Commission or other regulatory authorities. 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 March
31, 2018, 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.
US Prescribing Information for Yescarta,
including BOXED WARNING and Medication Guide, is available
at www.kitepharma.com and www.gilead.com.
For more information on Kite, please visit the
company’s website at www.kitepharma.com. Learn more about
Gilead 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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