-- 87 Percent of Patients in ZUMA-2 Pivotal
Trial Responded to Single Infusion of Tecartus --
-- Kite Becomes First Company with Multiple
Approved CAR T Therapies --
Kite, a Gilead Company (Nasdaq: GILD), today announced that the
U.S. Food and Drug Administration (FDA) has granted accelerated
approval to Tecartus™ (brexucabtagene autoleucel, formerly
KTE-X19), the first and only approved chimeric antigen receptor
(CAR) T cell therapy for the treatment of adult patients with
relapsed or refractory mantle cell lymphoma (MCL). The approval of
this one-time therapy follows a priority review and FDA
Breakthrough Therapy Designation and is based on results of ZUMA-2,
a single-arm, open-label study in which 87 percent of patients
responded to a single infusion of Tecartus, including 62 percent of
patients achieving a complete response (CR). Among patients
evaluable for safety, 18 percent experienced Grade 3 or higher
cytokine release syndrome (CRS) and 37 percent experienced Grade 3
or higher neurologic toxicities.
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“Despite promising advances, there are still major gaps in
treatment for patients with MCL who progress following initial
therapy,” said Michael Wang, MD, ZUMA-2 Lead Investigator and
Professor, Department of Lymphoma and Myeloma, Division of Cancer
Medicine at The University of Texas MD Anderson Cancer Center.
“Many patients have high-risk disease and are more likely to keep
progressing, even after subsequent treatments. The availability of
Tecartus as the first-ever cell therapy for patients with
relapsed/refractory MCL provides an important option with a
response rate of nearly 90 percent and early clinical evidence
suggesting durable remissions in later lines of therapy.”
“Kite is committed to bringing the promise of CAR T therapy to
patients with hematological cancers, and as such, we are proud to
launch our second cell therapy,” said Christi Shaw, Chief Executive
Officer of Kite. “I extend my thanks to the patient study
participants, caregivers, clinical researchers, regulators and
dedicated colleagues at Kite who helped make this approval
possible, and we look forward to partnering with the lymphoma
community to deliver this potentially transformative therapy to
patients with relapsed or refractory MCL.”
Tecartus has a Boxed Warning in its product label regarding the
risks of CRS and neurologic toxicities. A Risk Evaluation and
Mitigation Strategy (REMS) has been approved by the FDA for
Tecartus and has been combined with the Yescarta® (axicabtagene
ciloleucel) REMS. The REMS program will inform and educate
healthcare professionals about the risks associated with Tecartus
therapy, and training and certification on the REMS program will be
an integral part of the final authorization for centers offering
Tecartus. Additional information about the REMS program can be
found at www.YescartaTecartusREMS.com. Please see below for
Important Safety Information.
MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises
from cells originating in the “mantle zone” of the lymph node and
predominantly affects men over the age of 60. MCL is highly
aggressive following relapse, with many patients progressing
following therapy.
“This approval marks the first CAR T cell therapy approved for
mantle cell lymphoma patients and represents a new frontier in the
treatment of this disease,” said Meghan Gutierrez, Chief Executive
Officer at the Lymphoma Research Foundation. “In the past decade,
researchers have made significant progress in our understanding of
this disease and we have seen an increase in clinical trials for
patients, which we hope will continue to improve treatment
strategies and the options available to people with mantle cell
lymphoma. Today’s news builds upon this progress and provides hope
to mantle cell patients and their loved ones.”
Tecartus will be manufactured in Kite’s commercial manufacturing
facility in El Segundo, California. In the ZUMA-2 trial, Kite
demonstrated a 96 percent manufacturing success rate and a median
manufacturing turnaround time of 15 days from leukapheresis to
product delivery. Manufacturing speed is especially critical for
patients with advanced disease, who are very ill and at risk for
quick progression.
Patients whose healthcare professionals have prescribed Tecartus
therapy can work with Kite Konnect®, an integrated technology
platform that provides information and assistance throughout the
therapy process for Kite’s commercialized CAR T therapies,
including courier tracking for shipments and manufacturing status
updates. Kite Konnect provides support for eligible patients
receiving Yescarta and Tecartus, and it provides information for
the healthcare teams supporting their patients. Healthcare
providers and patients can reach Kite Konnect at
www.KiteKonnect.com or 1-844-454-KITE (1-844-454-5483).
KTE-X19 is currently under review in the European Union and has
been granted Priority Medicines (PRIME) designation by the European
Medicines Agency for relapsed or refractory MCL.
Tecartus Trial Results The
approval of Tecartus is supported by data from the ongoing, single
arm, open-label ZUMA-2 pivotal trial. The study enrolled 74 adult
patients with relapsed or refractory MCL who had previously
received anthracycline- or bendamustine-containing chemotherapy, an
anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor
(ibrutinib or acalabrutinib). The primary endpoint was objective
response rate (ORR) per the Lugano Classification (2014), defined
as the combined rate of CR and partial responses as assessed by an
Independent Radiologic Review Committee (IRRC).
In the study, 87 percent of patients (n=60 evaluable for
efficacy analysis) responded to a single infusion of Tecartus,
including 62 percent of patients who achieved a CR. Among all
patients, follow-up was at least six months after their first
objective disease response. Median duration of response has not yet
been reached.
In the trial, 18 percent of patients (n=82 evaluable for safety)
experienced Grade 3 or higher CRS and 37 percent experienced
neurologic events. The most common (≥ 10 percent) Grade 3 or higher
adverse reactions were anemia, neutropenia, thrombocytopenia,
hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia,
pyrexia, hyponatremia, hypertension, infection-pathogen
unspecified, pneumonia, hypocalcemia and lymphopenia. The FDA
approved Tecartus with a Risk Evaluation and Mitigation Strategy
(REMS). The Tecartus REMS has been combined with the Yescarta REMS
and is now called the “Yescarta (axicabtagene ciloleucel) and
Tecartus (brexucabtagene autoleucel) REMS Program”
(www.YescartaTecartusREMS.com).
About Tecartus Tecartus is
an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP™
manufacturing process that includes T cell enrichment, a necessary
step in certain B-cell malignancies in which circulating
lymphoblasts are a common feature. In addition to MCL, Tecartus is
also currently in Phase 1/2 trials in acute lymphoblastic leukemia
(ALL) and chronic lymphocytic leukemia (CLL). The use of Tecartus
in ALL and CLL is investigational, and its safety and efficacy have
not been established in these cancer types.
Tecartus Indication Tecartus
is a CD19-directed genetically modified autologous T cell
immunotherapy indicated for the treatment of adult patients with
relapsed or refractory mantle cell lymphoma (MCL).
This indication is approved under accelerated approval based on
overall response rate and durability of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY
INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC
TOXICITIES
- Cytokine Release Syndrome (CRS), including life-threatening
reactions, occurred in patients receiving Tecartus. Do not
administer Tecartus to patients with active infection or
inflammatory disorders. Treat severe or life-threatening CRS with
tocilizumab or tocilizumab and corticosteroids.
- Neurologic toxicities, including life-threatening reactions,
occurred in patients receiving Tecartus, including concurrently
with CRS or after CRS resolution. Monitor for neurologic toxicities
after treatment with Tecartus. Provide supportive care and/or
corticosteroids as needed.
- Tecartus 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), including
life-threatening reactions, occurred following treatment with
Tecartus. In ZUMA-2, CRS occurred in 91% (75/82) of patients
receiving Tecartus, including ≥ Grade 3 CRS in 18% of patients.
Among the patients who died after receiving Tecartus, one had a
fatal CRS event. The median time to onset of CRS was three days
(range: 1 to 13 days) and the median duration of CRS was ten days
(range: 1 to 50 days). Among patients with CRS, key manifestations
(>10%) included fever (99%), hypotension (60%), hypoxia (37%),
chills (33%), tachycardia (37%), headache (24%), fatigue (19%),
nausea (13%), alanine aminotransferase increased (13%), aspartate
aminotransferase increased (12%), and diarrhea (11%). Serious
events associated with CRS included hypotension, fever, hypoxia,
acute kidney injury, and tachycardia.
Ensure that a minimum of two doses of tocilizumab are available
for each patient prior to infusion of Tecartus. Following infusion,
monitor patients for signs and symptoms of CRS daily for at least
seven days at the certified healthcare facility, and for four 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, including those that were
life-threatening, occurred following treatment with Tecartus. In
ZUMA-2, neurologic events occurred in 81% of patients, 37% of whom
experienced Grade ≥3 adverse reactions. The median time to onset
for neurologic events was six days (range: 1 to 32 days).
Neurologic events resolved for 52 out of 66 (79%) patients with a
median duration of 21 days (range: 2 to 454 days). Three patients
had ongoing neurologic events at the time of death, including one
patient with serious encephalopathy. The remaining unresolved
neurologic events were either Grade 1 or Grade 2. Fifty-four (66%)
patients experienced CRS by the onset of neurological events. Five
(6%) patients did not experience CRS with neurologic events and
eight patients (10%) developed neurological events after the
resolution of CRS. 85% of all treated patients experienced the
first CRS or neurological event within the first seven days after
Tecartus infusion.
The most common neurologic events (>10%) included
encephalopathy (51%), headache (35%), tremor (38%), aphasia (23%),
and delirium (16%). Serious events including encephalopathy,
aphasia, and seizures occurred.
Monitor patients daily for at least seven days at the certified
healthcare facility and for four weeks following infusion for signs
and symptoms of neurologic toxicities and treat promptly.
REMS Program: Because of the risk of CRS and neurologic
toxicities, Tecartus is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
Yescarta and Tecartus REMS Program which requires that:
- Healthcare facilities that dispense and administer Tecartus
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 two hours after
Tecartus infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare
providers who prescribe, dispense, or administer Tecartus are
trained in the management of CRS and neurologic toxicities. Further
information is available at www.YescartaTecartusREMS.com or
1-844-454-KITE (5483).
Hypersensitivity Reactions: Serious hypersensitivity
reactions, including anaphylaxis, may occur due to dimethyl
sulfoxide (DMSO) or residual gentamicin in Tecartus.
Severe Infections: Severe or life-threatening infections
occurred in patients after Tecartus infusion. In ZUMA-2, infections
(all grades) occurred in 56% of patients. Grade 3 or higher
infections, including bacterial, viral, and fungal infections,
occurred in 30% of patients. Tecartus 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
antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients after
Tecartus 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 Tecartus
infusion. In ZUMA-2, Grade ≥3 cytopenias not resolved by Day 30
following Tecartus infusion occurred in 55% of patients and
included thrombocytopenia (38%), neutropenia (37%), and anemia
(17%). Monitor blood counts after infusion.
Hypogammaglobulinemia and B-cell aplasia can occur in
patients receiving treatment with Tecartus. In ZUMA-2,
hypogammaglobulinemia occurred in 16% of patients. Monitor
immunoglobulin levels after treatment with Tecartus and manage
using infection precautions, antibiotic prophylaxis, and
immunoglobulin replacement. The safety of immunization with live
viral vaccines during or following Tecartus treatment has not been
studied. Vaccination with live virus vaccines is not recommended
for at least six weeks prior to the start of lymphodepleting
chemotherapy, during treatment, and until immune recovery following
treatment with Tecartus.
Secondary Malignancies may develop. Monitor life-long for
secondary malignancies. In the event that it 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 Tecartus
infusion. Advise patients to refrain from driving and engaging in
hazardous activities, such as operating heavy or potentially
dangerous machinery, during this period.
Adverse Reactions: The most common adverse reactions
(incidence ≥ 20%) were pyrexia, CRS, hypotension, encephalopathy,
fatigue, tachycardia, arrhythmia, infection – pathogen unspecified,
chills, hypoxia, cough, tremor, musculoskeletal pain, headache,
nausea, edema, motor dysfunction, constipation, diarrhea, decreased
appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia.
Serious adverse reactions occurred in 66% of patients. The most
common serious adverse reactions (> 2%) were encephalopathy,
pyrexia, infection – pathogen unspecified, CRS, hypoxia, aphasia,
renal insufficiency, pleural effusion, respiratory failure,
bacterial infections, dyspnea, fatigue, arrhythmia, tachycardia,
and viral infections.
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. 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 physicians and patients may not see the
potential benefits of Tecartus therapy and the possibility of
unfavorable results from other ongoing and additional clinical
studies involving Tecartus for the treatment of adult patients with
relapsed or refractory MCL and other potential indications. There
is also the risk that the European Commission may not approve
KTE-X19 for the treatment of relapsed or refractory MCL in the
anticipated timelines or at all, and the marketing approval, if
granted, may have significant limitations on its use. 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, 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 Tecartus,
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Yescarta, Tecartus, XLP, and Kite Konnect 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20200724005428/en/
Douglas Maffei, PhD, Investors (650) 522-2739 Nathan
Kaiser, Media (650) 522-1853
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