-- Approval Marks Kite’s Fourth Indication
in Europe for its Two Cell Therapies and First in Leukemia
--
-- Overall Complete Remission of 71% and a
Median Overall Survival of More Than Two Years for All Patients and
Almost Four Years for Responders Demonstrated in ZUMA-3
Trial--
Kite, a Gilead Company (Nasdaq: GILD), today announced that the
European Commission (EC) has approved its CAR T-cell therapy
Tecartus® (brexucabtagene autoleucel) for the treatment of adult
patients 26 years of age and above with relapsed or refractory
(r/r) B-cell precursor acute lymphoblastic leukemia (ALL).
“This approval makes Tecartus the first and only CAR T-cell
therapy indicated for this population of patients, addressing a
significant unmet medical need,” said Christi Shaw, CEO, Kite.
“This is also the fourth indication in Europe for which a Kite cell
therapy is approved, clearly demonstrating the benefits they offer
to patients, especially those with limited treatment options.”
ALL is an aggressive type of blood cancer; the most common form
is B-cell precursor ALL. Globally, approximately 64,000 people are
diagnosed with ALL each year. Half of adults living with ALL will
relapse, and median overall survival (OS) with current
standard-of-care treatments is approximately just eight months.
“Adults with relapsed or refractory ALL often undergo multiple
treatments including chemotherapy, targeted therapy and stem cell
transplant, creating a significant burden on a patient’s quality of
life,” said Max S. Topp, MD, professor and head of Hematology,
University Hospital of Wuerzburg, Germany. “Patients in Europe now
have a meaningful advancement in treatment. Tecartus has
demonstrated durable responses, suggesting the potential for
long-term remission and a new approach to care.”
The approval is supported by data from the ZUMA-3 international
multicenter, single-arm, open-label, registrational Phase 1/2 study
of adult patients (≥18 years old) with relapsed or refractory ALL.
This study demonstrated that 71% of the evaluable patients (n=55)
achieved complete remission (CR) or CR with incomplete
hematological recovery (CRi) with a median follow-up of 26.8
months. In an extended data set of all pivotal dosed patients
(n=78) the median overall survival for all patients was more than
two years (25.4 months) and almost four years (47 months) for
responders (patients who achieved CR or CRi). Among
efficacy-evaluable patients, median duration of remission (DOR) was
18.6 months.
Among the patients treated with Tecartus at the target dose
(n=100) safety results were consistent with the known safety
profile for Tecartus. Grade 3 or higher cytokine release syndrome
(CRS) and neurologic adverse reactions occurred in 25% and 32% of
patients, respectively, and were generally well managed.
About ZUMA-3
ZUMA-3 is an ongoing international multicenter (US, Canada,
Europe), single arm, open label, registrational Phase 1/2 study of
Tecartus in adult patients (≥18 years old) with ALL whose disease
is refractory to or has relapsed following standard systemic
therapy or hematopoietic stem cell transplantation. The primary
endpoint is the rate of overall complete remission or complete
remission with incomplete hematological recovery by central
assessment. Duration of remission and relapse-free survival,
overall survival, minimal residual disease (MRD) negativity rate,
and allo-SCT rate were assessed as secondary endpoints.
About Acute Lymphoblastic
Leukemia
ALL is an aggressive type of blood cancer that develops when
abnormal white blood cells accumulate in the bone marrow until
there isn’t any room left for blood cells to form. In some cases,
these abnormal cells invade healthy organs and can also involve the
lymph nodes, spleen, liver, central nervous system and other
organs.
About Tecartus
Please see full FDA Prescribing Information, including BOXED
WARNING and Medication Guide.
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.
- Adult patients with relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL).
U.S. 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 92% (72/78) of patients with
ALL, including ≥ Grade 3 (Lee grading system 1) CRS in 26% of
patients. Three patients with ALL had ongoing CRS events at the
time of death. The median time to onset of CRS was five days
(range: 1 to 12 days) and the median duration of CRS was eight days
(range: 2 to 63 days) for patients with ALL.. Among patients with
CRS, the key manifestations (>10%) were similar in MCL and ALL
and included fever (93%), hypotension (62%), tachycardia (59%),
chills (32%), hypoxia (31%), headache (21%), fatigue (20%), and
nausea (13%). Serious events associated with CRS included
hypotension, fever, hypoxia, tachycardia, and dyspnea.
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 for patients with MCL and at least 14 days for patients
with ALL 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 Events, including those that were fatal or
life-threatening, occurred following treatment with Tecartus.
Neurologic events occurred in 81% (66/82) of patients with MCL,
including ≥ Grade 3 in 37% of patients. The median time to onset
for neurologic events was six days (range: 1 to 32 days) with a
median duration of 21 days (range: 2 to 454 days) in patients with
MCL. Neurologic events occurred in 87% (68/78) of patients with
ALL, including ≥ Grade 3 in 35% of patients. The median time to
onset for neurologic events was seven days (range: 1 to 51 days)
with a median duration of 15 days (range: 1 to 397 days) in
patients with ALL. For patients with MCL, 54 (66%) patients
experienced CRS before 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. Neurologic events resolved for 119 out of 134 (89%)
patients treated with Tecartus. Nine patients (three patients with
MCL and six patients with ALL) had ongoing neurologic events at the
time of death. For patients with ALL, neurologic events occurred
before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of
patients; respectively. Three patients (4%) had neurologic events
without CRS. The onset of neurologic events can be concurrent with
CRS, following resolution of CRS or in the absence of CRS.
The most common neurologic events (>10%) were similar in MCL
and ALL and included encephalopathy (57%), headache (37%), tremor
(34%), confusional state (26%), aphasia (23%), delirium (17%),
dizziness (15%), anxiety (14%), and agitation (12%). Serious events
including encephalopathy, aphasia, confusional state, and seizures
occurred after treatment with Tecartus.
Monitor patients daily for at least seven days for patients with
MCL and at least 14 days for patients with ALL 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. Infections (all
grades) occurred in 56% (46/82) of patients with MCL and 44%
(34/78) of patients with ALL. Grade 3 or higher infections,
including bacterial, viral, and fungal infections, occurred in 30%
of patients with ALL and MCL. Tecartus should not be administered
to patients with clinically significant active systemic infections.
Monitor patients for signs and symptoms of infection before and
after Tecartus infusion and treat appropriately. Administer
prophylactic antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients with MCL and
35% of patients with ALL after Tecartus infusion and may be
concurrent with CRS. The febrile neutropenia in 27 (35%) of
patients with ALL includes events of “febrile neutropenia” (11
(14%)) plus the concurrent events of “fever” and “neutropenia” (16
(21%)). In the event of febrile neutropenia, evaluate for infection
and manage with broad spectrum antibiotics, fluids, and other
supportive care as medically indicated.
In immunosuppressed patients, life-threatening and fatal
opportunistic infections have been reported. The possibility of
rare infectious etiologies (e.g., fungal and viral infections such
as HHV-6 and progressive multifocal leukoencephalopathy) should be
considered in patients with neurologic events and appropriate
diagnostic evaluations should be performed.
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 patients with MCL, Grade 3 or higher cytopenias not
resolved by Day 30 following Tecartus infusion occurred in 55%
(45/82) of patients and included thrombocytopenia (38%),
neutropenia (37%), and anemia (17%). In patients with ALL who were
responders to Tecartus treatment, Grade 3 or higher cytopenias not
resolved by Day 30 following Tecartus infusion occurred in 20%
(7/35) of the patients and included neutropenia (12%) and
thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved
by Day 60 following Tecartus infusion occurred in 11% (4/35) of the
patients and included neutropenia (9%) and thrombocytopenia (6%).
Monitor blood counts after Tecartus infusion.
Hypogammaglobulinemia: B cell aplasia and
hypogammaglobulinemia can occur in patients receiving treatment
with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of
patients with MCL and 9% (7/78) of patients with ALL. 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 Tecartus
treatment, and until immune recovery following treatment with
Tecartus.
Secondary Malignancies may develop. Monitor life-long for
secondary malignancies. In the event that one 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 non-laboratory adverse
reactions (≥ 20%) were fever, cytokine release syndrome,
hypotension, encephalopathy, tachycardia, nausea, chills, headache,
fatigue, febrile neutropenia, diarrhea, musculoskeletal pain,
hypoxia, rash, edema, tremor, infection with pathogen unspecified,
constipation, decreased appetite, and vomiting. The most common
serious adverse reactions (≥ 2%) were cytokine release syndrome,
febrile neutropenia, hypotension, encephalopathy, fever, infection
with pathogen unspecified, hypoxia, tachycardia, bacterial
infections, respiratory failure, seizure, diarrhea, dyspnea, fungal
infections, viral infections, coagulopathy, delirium, fatigue,
hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema,
and paraparesis.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company
based in Santa Monica, California, with manufacturing operations in
North America and Europe. Kite’s singular focus is cell therapy to
treat and potentially cure cancer. As the cell therapy leader, Kite
has more approved CAR T indications to help more patients than any
other company. For more information on Kite, please visit
www.kitepharma.com. Follow Kite on social media on Twitter
(@KitePharma) and LinkedIn.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis and cancer. Gilead operates in more than 35
countries worldwide, with headquarters in Foster City,
California.
Forward-Looking
Statements
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 ability of Gilead and Kite to initiate, progress or
complete clinical trials within currently anticipated timelines or
at all, and the possibility of unfavorable results from ongoing and
additional clinical trials, including those involving Tecartus; the
risk that physicians may not see the benefits of prescribing
Tecartus for the treatment of blood cancers; and any assumptions
underlying any of the foregoing. These and other risks,
uncertainties and other factors are described in detail in Gilead’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2022
as filed with the U.S. Securities and Exchange Commission. These
risks, uncertainties and other factors could cause actual results
to differ materially from those referred to in the forward-looking
statements. All statements other than statements of historical fact
are statements that could be deemed forward-looking statements. The
reader is cautioned that any such forward-looking statements are
not guarantees of future performance and involve risks and
uncertainties and is cautioned not to place undue reliance on these
forward-looking statements. 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.
U.S. Prescribing Information for Tecartus
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Kite, the Kite logo, Tecartus and GILEAD are
trademarks of Gilead Sciences, Inc. or its related companies.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220906006101/en/
Jacquie Ross, Investors investor_relations@gilead.com
Anna Padula, Media apadula@kitepharma.com
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