– Pivotal ZUMA-5 Study Demonstrates Overall
Response Rate of 91% and a Complete Response rate of 77% in
Patients Who Received Yescarta After Three or More Lines of
Therapy –
– Kite’s Third Approved Cell Therapy
Indication in Europe –
Kite, a Gilead Company (Nasdaq: GILD), today announces that the
European Commission (EC) has approved its CAR T-cell therapy
Yescarta® (axicabtagene ciloleucel) for the treatment of
adult patients with relapsed or refractory follicular lymphoma (FL)
after three or more lines of systemic therapy. Yescarta has
maintained orphan medicinal product designation in this
indication.
“Patients with advanced relapsed or refractory follicular
lymphoma have a high need for new treatment options,” said Christi
Shaw, CEO, Kite. “This is the third approved indication for a Kite
cell therapy in Europe, and we are pleased to enable more patients
with different lymphomas greater access to this treatment
innovation.”
Follicular lymphoma is a form of non-Hodgkin lymphoma in which
tumors grow slowly but can become more aggressive over time. FL is
the second most common type of lymphoma globally and accounts for
approximately 22% of all lymphomas diagnosed worldwide. In Europe,
approximately 27,000 new cases are diagnosed each year.
“Follicular lymphoma that has relapsed multiple times is a
difficult-to-treat disease with an especially poor prognosis as
only 20% of patients are still alive at five years after their
second relapse,” said Ibrahim Yakoub-Agha, MD, PhD, Head of the
Hematopoietic Cell Transplantation and Cellular Therapy Unit, Lille
University Hospital. “Ninety-one percent of patients in the ZUMA-5
study responded to axicabtagene ciloleucel after three or more
prior lines of therapy, and more than half of these were still in
response two years later. This sign of durable remission is
critical for patients who need options that can deliver long-term
benefit.”
“Follicular lymphoma is often misunderstood as easy to treat or
non life-threatening, even when it has reached a significantly
advanced stage,” said Nicola Mendelsohn, Founder and Chair of the
Follicular Lymphoma Foundation (FLF). “For patients with later-line
relapsed or refractory disease, it is often very aggressive.
Axicabtagene ciloleucel represents an important advance for a
patient population in Europe with limited treatment options.”
The approval is supported by data from the pivotal, single-arm
Phase 2 ZUMA-5 international study in patients with relapsed or
refractory FL who had received at least two prior lines of systemic
therapy, including the combination of an anti-CD20 monoclonal
antibody and an alkylating agent. Among patients who had received
three or more lines of prior therapy (n=75), the overall response
rate (ORR) was 91%, and the complete response (CR) rate was 77% at
the 24-month analysis. The median duration of response (DoR) was
38.6 months, and the proportion of responders still in response at
Month 24 was 56%.
Among all evaluable patients within ZUMA-5 (n=119), safety
observations were consistent with the known safety profile for
Yescarta. Grade ≥3 cytokine release syndrome (CRS) occurred in 6%
of patients and neurologic events occurred 16% of patients. Most
CRS cases (99%) of any grade resolved by the time of data cut-off
and 60% of neurologic events were resolved within three weeks. The
most significant and frequently occurring adverse events were CRS
(77%), infections (59%) and encephalopathy (47%). For full details
on the Special Warnings and Precautions for Use and Adverse
Reactions (including appropriate management), please refer to the
EU Summary of Product Characteristics (SmPC).
Additional data were shared separately during an oral
presentation at the 2021 American Society of Hematology
Meeting.
About Follicular
Lymphoma
FL is a form of indolent non-Hodgkin lymphoma (iNHL) in which
malignant tumors slowly grow but can become more aggressive over
time, especially if they relapse. FL is the most common form of
indolent non-Hodgkin lymphoma and the second most common type of
lymphoma globally. It accounts for approximately 22% of all
lymphomas diagnosed worldwide. Currently, there are limited options
for the treatment of relapsed or refractory FL after two or more
lines of therapy.
About ZUMA-5
ZUMA-5 is an ongoing, single-arm, open-label, international,
multicentre trial evaluating 122 patients (≥18 years old) with
relapsed or refractory follicular lymphoma (FL), who received at
least two prior lines of systemic therapy, including the
combination of an anti-CD20 monoclonal antibody and an alkylating
agent. The primary endpoint was ORR, and secondary endpoints
included CR rate, ORR and CR in patients who had received three or
more lines of prior therapy, DoR, overall survival,
progression-free survival and incidence of adverse events.
About Yescarta
Please see full US Prescribing Information, including BOXED
WARNING and Medication Guide.
YESCARTA is a CD19-directed genetically modified autologous T
cell immunotherapy indicated for the treatment of:
- Adult patients with large B-cell lymphoma that is refractory to
first-line chemoimmunotherapy or that relapses within 12 months of
first-line chemoimmunotherapy.
- 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. Limitations of Use: YESCARTA is not indicated for
the treatment of patients with primary central nervous system
lymphoma.
- Adult patients with relapsed or refractory follicular lymphoma
(FL) after two or more lines of systemic therapy. This indication
is approved under accelerated approval based on the response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the
confirmatory trial(s).
U.S. IMPORTANT SAFETY INFORMATION
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 and TECARTUS REMS Program.
CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred.
CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma
(NHL), including ≥ Grade 3 in 9%. CRS occurred in 93% (256/276) of
patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in
9%. Among patients with LBCL who died after receiving YESCARTA, 4
had ongoing CRS events at the time of death. For patients with LBCL
in ZUMA-1, the median time to onset of CRS was 2 days following
infusion (range: 1-12 days) and the median duration was 7 days
(range: 2-58 days). For patients with LBCL in ZUMA-7, the median
time to onset of CRS was 3 days following infusion (range: 1-10
days) and the median duration was 7 days (range: 2-43 days). CRS
occurred in 84% (123/146) of patients with indolent non-Hodgkin
lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 in 8%. Among
patients with iNHL who died after receiving YESCARTA, 1 patient had
an ongoing CRS event at the time of death. The median time to onset
of CRS was 4 days (range: 1-20 days) and the median duration was 6
days (range: 1-27 days) for patients with iNHL.
Key manifestations of CRS (≥ 10%) in all patients combined
included fever (85%), hypotension (40%), tachycardia (32%), chills
(22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious
events that may be associated with CRS include cardiac arrhythmias
(including atrial fibrillation and ventricular tachycardia), renal
insufficiency, cardiac failure, respiratory failure, cardiac
arrest, capillary leak syndrome, multi-organ failure, and
hemophagocytic lymphohistiocytosis/macrophage activation
syndrome.
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of CRS was assessed in 2 subsequent cohorts
of LBCL patients in ZUMA-1. Among patients who received tocilizumab
and/or corticosteroids for ongoing Grade 1 events, CRS occurred in
93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients
experienced a Grade 4 or 5 event. The median time to onset of CRS
was 2 days (range: 1-8 days) and the median duration of CRS was 7
days (range: 2-16 days). Prophylactic treatment with
corticosteroids was administered to a cohort of 39 patients for 3
days beginning on the day of infusion of YESCARTA. Thirty-one of
the 39 patients (79%) developed CRS and were managed with
tocilizumab and/or therapeutic doses of corticosteroids with no
patients developing ≥ Grade 3 CRS. The median time to onset of CRS
was 5 days (range: 1-15 days) and the median duration of CRS was 4
days (range: 1-10 days). Although there is no known mechanistic
explanation, consider the risk and benefits of prophylactic
corticosteroids in the context of pre-existing comorbidities for
the individual patient and the potential for the risk of Grade 4
and prolonged neurologic toxicities.
Ensure that 2 doses of tocilizumab are available prior to
YESCARTA infusion. Monitor patients for signs and symptoms of CRS
at least daily for 7 days at the certified healthcare facility, and
for 4 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
Neurologic toxicities (including immune effector cell-associated
neurotoxicity syndrome) that were fatal or life-threatening
occurred. Neurologic toxicities occurred in 78% (330/422) of all
patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%.
Neurologic toxicities occurred in 87% (94/108) of patients with
LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of
patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to
onset was 4 days (range: 1-43 days) and the median duration was 17
days for patients with LBCL in ZUMA-1. The median time to onset for
neurologic toxicity was 5 days (range:1- 133 days) and the median
duration was 15 days in patients with LBCL in ZUMA-7. Neurologic
toxicities occurred in 77% (112/146) of patients with iNHL,
including ≥ Grade 3 in 21%. The median time to onset was 6 days
(range: 1-79 days) and the median duration was 16 days.
Ninety-eight percent of all neurologic toxicities in patients with
LBCL and 99% of all neurologic toxicities in patients with iNHL
occurred within the first 8 weeks of YESCARTA infusion. Neurologic
toxicities occurred within the first 7 days of infusion for 87% of
affected patients with LBCL and 74% of affected patients with
iNHL.
The most common neurologic toxicities (≥ 10%) in all patients
combined included encephalopathy (50%), headache (43%), tremor
(29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia
(10%). Prolonged encephalopathy lasting up to 173 days was noted.
Serious events, including aphasia, leukoencephalopathy, dysarthria,
lethargy, and seizures occurred. Fatal and serious cases of
cerebral edema and encephalopathy, including late-onset
encephalopathy, have occurred.
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of neurologic toxicities was assessed in 2
subsequent cohorts of LBCL patients in ZUMA-1. Among patients who
received corticosteroids at the onset of Grade 1 toxicities,
neurologic toxicities occurred in 78% (32/41), and 20% (8/41) had
Grade 3 neurologic toxicities; no patients experienced a Grade 4 or
5 event. The median time to onset of neurologic toxicities was 6
days (range: 1-93 days) with a median duration of 8 days (range:
1-144 days). Prophylactic treatment with corticosteroids was
administered to a cohort of 39 patients for 3 days beginning on the
day of infusion of YESCARTA. Of those patients, 85% (33/39)
developed neurologic toxicities, 8% (3/39) developed Grade 3, and
5% (2/39) developed Grade 4 neurologic toxicities. The median time
to onset of neurologic toxicities was 6 days (range: 1-274 days)
with a median duration of 12 days (range: 1-107 days). Prophylactic
corticosteroids for management of CRS and neurologic toxicities may
result in a higher grade of neurologic toxicities or prolongation
of neurologic toxicities, delay the onset of and decrease the
duration of CRS.
Monitor patients for signs and symptoms of neurologic toxicities
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter, and treat promptly.
REMS
Because of the risk of CRS and neurologic toxicities, YESCARTA
is available only through a restricted program called the YESCARTA
and TECARTUS REMS Program which requires that: Healthcare
facilities that dispense and administer YESCARTA must be enrolled
and comply with the REMS requirements and must have on-site,
immediate access to a minimum of 2 doses of tocilizumab 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 in the management of CRS and
neurologic toxicities. Further information is available at
www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS
Allergic reactions, including serious hypersensitivity reactions
or anaphylaxis, may occur with the infusion of YESCARTA.
SERIOUS INFECTIONS
Severe or life-threatening infections occurred. Infections (all
grades) occurred in 45% of patients with NHL; ≥ Grade 3 infections
occurred in 17% of patients, including ≥ Grade 3 infections with an
unspecified pathogen in 12%, bacterial infections in 5%, viral
infections in 3%, and fungal infections in 1%. YESCARTA 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 36% of all patients with NHL
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.
In immunosuppressed patients, including those who have received
YESCARTA, life-threatening and fatal opportunistic infections
including disseminated fungal infections (e.g., candida sepsis and
aspergillus infections) and viral reactivation (e.g., human herpes
virus-6 [HHV-6] encephalitis and JC virus progressive multifocal
leukoencephalopathy [PML]) have been reported. The possibility of
HHV-6 encephalitis and PML should be considered in immunosuppressed
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, including
YESCARTA. 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
cytopenias not resolved by Day 30 following YESCARTA infusion
occurred in 39% of all patients with NHL and included neutropenia
(33%), thrombocytopenia (13%), and anemia (8%). Monitor blood
counts after infusion.
HYPOGAMMAGLOBULINEMIA
B-cell aplasia and hypogammaglobulinemia can occur.
Hypogammaglobulinemia was reported as an adverse reaction in 14% of
all patients with NHL. 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
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
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 non-laboratory adverse reactions (incidence ≥
20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue,
hypotension, encephalopathy, tachycardia, diarrhea, headache,
musculoskeletal pain, nausea, febrile neutropenia, chills, cough,
infection with an unspecified pathogen, dizziness, tremor,
decreased appetite, edema, hypoxia, abdominal pain, aphasia,
constipation, and vomiting.
The most common adverse reactions (incidence ≥ 20%) in patients
with LBCL in ZUMA-1 included CRS, fever, hypotension,
encephalopathy, tachycardia, fatigue, headache, decreased appetite,
chills, diarrhea, febrile neutropenia, infections with an
unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness,
constipation, and cardiac arrhythmias.
The most common non-laboratory adverse reactions (incidence ≥
20%) in patients with iNHL in ZUMA-5 included fever, CRS,
hypotension, encephalopathy, fatigue, headache, infections with an
unspecified, tachycardia, febrile neutropenia, musculoskeletal
pain, nausea, tremor, chills, diarrhea, constipation, decreased
appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.
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 Kite and Gilead 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 Yescarta; the
risk that physicians may not see the benefits of prescribing
Yescarta for the treatment of FL; 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 March 31, 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 Kite and Gilead,
and Kite and Gilead assume no obligation and disclaim any intent to
update any such forward-looking statements.
U.S. Prescribing Information for Yescarta
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Kite, the Kite logo, Yescarta, and GILEAD are
trademarks of Gilead Sciences, Inc. or its related companies.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220628005521/en/
Jacquie Ross, Investors investor_relations@gilead.com
Anna Padula, Media apadula@kitepharma.com
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