-- 42 Percent of Patients Remained in
Response, Including 40 Percent in Complete Remission, at a Median
Follow-up of 15.4 Months --
-- Data Presented at the Annual Meeting of
the American Society of Hematology and Published in The New England
Journal of Medicine --
Kite, a Gilead Company (Nasdaq: GILD), announced long-term
follow-up data from the pivotal ZUMA-1 study of Yescarta™
(axicabtagene ciloleucel) in patients with refractory large B-cell
lymphoma. With a minimum follow-up of one year after a single
infusion of Yescarta (median follow-up of 15.4 months), 42 percent
of patients continued to respond to therapy, including 40 percent
with a complete remission. Detailed results from this updated
analysis were simultaneously presented at the Annual Meeting of the
American Society of Hematology (ASH) in Atlanta and published in
The New England Journal of Medicine.
This press release features multimedia. View
the full release here:
http://www.businesswire.com/news/home/20171210005072/en/
Yescarta is the first chimeric antigen receptor T (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 patients with primary
central nervous system lymphoma.
DLBCL is the most common aggressive non-Hodgkin lymphoma,
accounting for three out of every five cases. In the United States
each year, there are approximately 7,500 patients with refractory
DLBCL who are eligible for CAR T therapy.
“As observed in the SCHOLAR-1 study, treatment options for
patients with refractory large B-cell lymphoma have yielded a
median overall survival of just six months, with fewer than ten
percent of patients achieving complete remission,” said Sattva S.
Neelapu, MD, ZUMA-1 Co-Lead Investigator and Professor,
Department of Lymphoma/Myeloma, Division of Cancer Medicine
at The University of Texas MD Anderson Cancer Center. “The
durability of response seen with Yescarta in this long-term
follow-up reinforces the major advance that CAR T therapy
represents for these patients.”
To evaluate the durability of Yescarta responses, an updated
analysis was conducted when patients in ZUMA-1 had been followed
for a minimum of one year (n=108). In this updated analysis, 82
percent of patients had responded to Yescarta, including 58 percent
of patients who had achieved complete remission. At a median of
15.4 months post-infusion, 42 percent of patients remained in
response, including 40 percent in complete remission. The median
duration of response was 11.1 months (95 percent CI: 3.9 months to
not estimable [NE]); in patients who have achieved a complete
remission, the median duration of response was not reached (95
percent CI: NE). Median overall survival had not been reached (95
percent CI: 12 months to NE) with an overall survival rate at 18
months of 52 percent (95 percent CI: 41 to 62).
In the updated analysis, 12 percent of patients experienced
Grade 3 or higher cytokine release syndrome (CRS) and 31 percent
experienced neurologic toxicities respectively. The most common
Grade 3 or higher reactions were neutropenia (79 percent), anemia
(45 percent) and thrombocytopenia (40 percent). Ten patients
experienced a serious adverse event six months after Yescarta
infusion, including eight patients with infections. No new onset
CRS or neurologic events related to Yescarta were observed in the
updated analysis.
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.
“Historically, people with refractory large B-cell lymphoma have
not been adequately served by available treatment options,” said
David Chang, MD, PhD, Worldwide Head of Research and Development
and Chief Medical Officer at Kite. “We are encouraged by the
durability and depth of response seen in ZUMA-1 more than a year
after treatment with Yescarta, which represents an important
advance in the treatment of patients with refractory disease.”
Yescarta has been granted Priority Medicines (PRIME) regulatory
support for DLBCL in the European Union. A Marketing Authorization
Application (MAA) for axicabtagene ciloleucel is currently under
review with the European Medicines Agency (EMA) and potential
approval is expected in the first half of 2018.
U.S. Indication for
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.
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 REMS.
Cytokine Release Syndrome (CRS)
CRS, including fatal or life-threatening reactions, occurred
following treatment with Yescarta. In Study 1, CRS occurred in 94%
(101/108) of patients receiving Yescarta, including ≥ Grade 3 (Lee
grading system) CRS in 13% (14/108) of patients. Among patients who
died after receiving Yescarta, four had ongoing CRS events at the
time of death. The median time to onset was 2 days (range: 1 to 12
days) and the median duration of CRS was 7 days (range: 2 to 58
days). Key manifestations of CRS 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 (HLH/MAS).
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, that were fatal or life-threatening,
occurred following treatment with Yescarta. Neurologic toxicities
occurred in 87% of patients. Ninety-eight percent of all neurologic
toxicities occurred within the first 8 weeks of Yescarta infusion,
with a median time to onset of 4 days (range: 1 to 43 days). The
median duration of neurologic toxicities was 17 days. Grade 3 or
higher neurologic toxicities 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 two
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 with the infusion of Yescarta.
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 in patients after
Yescarta infusion. In Study 1, infections (all grades) occurred in
38% of patients. Grade 3 or higher infections occurred in 23% of
patients. 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 after
Yescarta infusion 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.
Viral Reactivation
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. In Study 1,
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 in patients
receiving treatment with Yescarta. In Study 1,
hypogammaglobulinemia occurred in 15% of patients. Monitor
immunoglobulin levels after treatment with Yescarta 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 with
Yescarta.
Secondary Malignancies
Patients treated with Yescarta 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 receiving Yescarta 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. Serious
adverse reactions occurred in 52% of patients. The most common
serious adverse reactions (> 2%) include encephalopathy, fever,
lung infection, febrile neutropenia, cardiac arrhythmia, cardiac
failure, urinary tract infection, renal insufficiency, aphasia,
cardiac arrest, Clostridium difficile infection, delirium,
hypotension, and hypoxia.
The most common (≥ 10%) Grade 3 or higher reactions include
febrile neutropenia, fever, CRS, encephalopathy,
infections-pathogen unspecified, hypotension, hypoxia and lung
infections.
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 is a biopharmaceutical company that
discovers, develops and commercializes innovative therapeutics in
areas of unmet medical need. The company’s mission is to advance
the care of patients suffering from life-threatening diseases.
Gilead has operations in more than 30 countries worldwide, with
headquarters in Foster City, California.
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 possibility of unfavorable results from further
clinical trials involving Yescarta. In addition, regulatory
agencies, including the EMA, may not approve Yescarta in the
currently anticipated timelines or at all, and any marketing
approvals may have significant limitations on its use. All
statements other than statements of historical fact are statements
that could be deemed forward-looking statements. Investors are
cautioned that any such forward-looking statements are not
guarantees of future performance and involve risks and
uncertainties and are cautioned not to place undue reliance on
these forward-looking statements. Actual results may differ
materially from those currently anticipated due to a number of
risks and uncertainties. Risks and uncertainties that could cause
the actual results to differ from expectations contemplated by
forward-looking statements include risks and uncertainties detailed
from time to time in Gilead Sciences, Inc.’s Quarterly Report on
Form 10-Q for the quarter ended September 30, 2017 as filed with
the 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 and disclaim any
intent to update any such forward-looking statements.
US Prescribing Information for Yescarta,
including BOXED WARNING and Medication Guide, is available
at www.yescarta.com.
For more information on Gilead Sciences,
please visit the company’s website at www.gilead.com, follow
Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20171210005072/en/
Gilead SciencesSung Lee, 650-524-7792InvestorsorNathan Kaiser,
650-522-1853Media
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Mar 2024 to Apr 2024
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Apr 2023 to Apr 2024