— New Safety Data Involving Steroid Use and New Subpopulation
Analyses from Pivotal ZUMA-1 Trial to Provide Greater Understanding of
Yescarta® in Patients with
Relapsed or Refractory Large B-cell Lymphoma —
— End of Phase 1 Results from ZUMA-3 Evaluating KTE-X19 in Adults
with Relapsed or Refractory Acute Lymphoblastic Leukemia to be Presented
SANTA MONICA, Calif.–(BUSINESS WIRE)–Kite, a Gilead Company (Nasdaq: GILD), today announced that new data
from its cell therapy programs will be presented at the 55th Annual
Meeting of the American Society of Clinical Oncology (ASCO) being held
in Chicago from May 31 – June 4, 2019. Six abstracts highlighting
updated Yescarta® (axicabtagene ciloleucel) efficacy and
safety results, and ongoing research from the company’s chimeric antigen
receptor T (CAR T) cell therapy development program in hematologic
malignancies will be presented at the meeting.
“Our CAR T research program is progressing at a rapid pace and we are
excited to share the latest data at ASCO,” said John McHutchison, AO,
MD, Chief Scientific Officer and Head of Research and Development,
Gilead Sciences. “Our data at this year’s meeting will include new
analyses from the pivotal ZUMA-1 trial of Yescarta, early results from a
novel approach to improve the Yescarta safety profile and results from
the ZUMA-3 trial of our investigational CAR T therapy KTE-X19 in adults
with acute lymphoblastic leukemia. These findings will help physicians
better assess the potential role of CAR T in patients with high unmet
need and continue to build upon our understanding of cell therapy.”
Data from the ZUMA CAR T cell therapy development program to be
presented at the meeting include new results evaluating earlier steroid
use on the rates of adverse events in patients with relapsed or
refractory large B-cell lymphoma treated with Yescarta, as well as a
separate subpopulation analysis of efficacy and safety results in
refractory large B-cell lymphoma patients over the age of 65 in the
ZUMA-1 trial. End of Phase 1 data from the ZUMA-3 trial of
investigational KTE-X19 in adult patients with relapsed or refractory
acute lymphoblastic leukemia (ALL) will also be presented.
Details on Kite cell therapy data to be presented at the meeting include:
Area of Focus, Presentation
Acute Lymphoblastic Leukemia
End of Phase 1 Results of ZUMA-3, a Phase 1/2 Study of KTE-X19,
Anti-CD19 Chimeric Antigen Receptor T Cell Therapy, in Adult
Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
Large B-Cell Lymphoma
Outcomes of Patients ≥ 65 Years of Age in ZUMA-1, a Pivotal Phase
1/2 Study of Axicabtagene Ciloleucel in Refractory Large B-Cell
Large B-Cell Lymphoma
Preliminary Results of Earlier Steroid Use with Axicabtagene
Ciloleucel in Patients with Relapsed/Refractory Large B-Cell Lymphoma
Large B-Cell Lymphoma
Hematopoietic Recovery and Immune Reconstitution After Axicabtagene
Ciloleucel Chimeric Antigen Receptor T Cell Therapy in Patients with
Relapsed/Refractory Large B-cell Lymphoma
Chronic Lymphocytic Leukemia
ZUMA-8: A Phase 1/2 Multicenter Study Evaluating KTE-X19 in Patients
with Relapsed/Refractory Chronic Lymphocytic Leukemia
Large B-Cell Lymphoma
ZUMA-12: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel as a
First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma
For more information, including a complete list of abstract titles at
the meeting, please visit: https://meetinglibrary.asco.org/.
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, and 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. The Yescarta U.S.
Prescribing Information has a BOXED WARNING for the risks of cytokine
release syndrome and neurologic toxicities; see below for Important
KTE-X19 is an investigational agent that has not been approved by the
U.S. Food and Drug Administration or any regulatory authority for any
uses. Efficacy and safety have not yet been established.
U.S. Important Safety Information for Yescarta
BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC
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
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
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.
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.
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
possibility of unfavorable results from ongoing and additional clinical
trials involving Yescarta or KTE-X19. 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, 2019, 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.
Yescarta is a registered trademark of Gilead Sciences,
Inc., or its related companies.
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.
Sung Lee, Investors
Nathan Kaiser, Media