Market Overview

Kite Announces Long-Term Data From Pivotal ZUMA-1 Study of Yescarta™ (Axicabtagene Ciloleucel) in Patients With Refractory Large B-cell Lymphoma

Share:

-- 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 Comments and Join the Discussion!