New indication for this one-time infusion may
provide patients with a treatment-free respite as early as first
relapse
Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a
global leader in cell therapy, announced today the U.S. Food and
Drug Administration (FDA) has approved CARVYKTI® (ciltacabtagene
autoleucel; cilta-cel) for the treatment of patients with relapsed
or refractory multiple myeloma who have received at least one prior
line of therapy, including a proteasome inhibitor (PI), and an
immunomodulatory agent (IMiD), and are refractory to lenalidomide.1
CARVYKTI® is the first and only B-cell Maturation Antigen (BCMA)
targeted therapy, including CAR-T therapies, bispecific antibodies,
and antibody-drug conjugates (ADCs), approved starting in the
second-line of treatment for patients with multiple myeloma.
“The expanded label of CARVYKTI has the potential to transform
the treatment paradigm for multiple myeloma by providing patients
and physicians with a personalized immunotherapy that can be used
earlier in the treatment regimen. Multiple myeloma is an incurable
and progressive hematologic cancer that causes patients to relapse
and become refractory to treatment, so new, innovative options are
desperately needed,” said Ying Huang, Ph.D., Chief Executive
Officer of Legend Biotech. “We are committed to improving the lives
of patients battling blood cancer and will continue to work towards
developing cellular therapies that bring us closer to a cure.”
The FDA approval is based on positive results from the
CARTITUDE-4 study, which demonstrated that CARVYKTI® resulted in
statistically significant and clinically meaningful improvement of
progression-free survival compared to two standard of care
treatment regimens, pomalidomide, bortezomib, and dexamethasone
(PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), in
adults with relapsed and lenalidomide-refractory multiple myeloma
who received one to three prior lines of therapy.1 This approval
follows a unanimous (11 to 0) recommendation from the FDA Oncologic
Drugs Advisory Committee (ODAC) in support of CARVYKTI® in earlier
lines of treatment.
“The results of the CARTITUDE-4 study demonstrated the
substantial clinical benefit of cilta-cel infusion over standard of
care continuous therapy in patients who experience a relapse after
one to three prior treatments,” said Surbhi Sidana, M.D., Assistant
Professor of Medicine, Blood and Marrow Transplantation &
Cellular Therapy at Stanford University School of Medicine.† “This
expanded FDA approval for cilta-cel will allow a wider patient
population to access this novel therapy earlier in the course of
their treatment.”
“This expanded FDA approval validates the growing need for
CARVYKTI and means more patients will have access to our
life-altering, individualized therapy,” said Birk Vanderweeën,
Senior Vice President, Global Manufacturing and Supply. “To ensure
we can meet increased demand for our customized therapy, our global
manufacturing teams and partners have expanded production capacity
and are laser-focused on further scaling out operations to ensure
patients who need CARVYKTI have access to it.”
The safety profile for CARVYKTI® includes a boxed warning for
Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barre
syndrome, and their associated complications, Hemophagocytic
Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS),
Prolonged and Recurrent Cytopenias and Secondary Malignancies
including myelodysplastic syndrome, acute myeloid leukemia, and
T-cell malignancies.1 Warnings and Precautions include Increased
Early Mortality, Infections, Hypogammaglobulinemia,
Hypersensitivity Reactions, and Effects on Ability to Drive and Use
Machines.1
The most common nonlaboratory adverse reactions (incidence
greater than 20%) are pyrexia, cytokine release syndrome,
hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue,
infections-pathogen unspecified, cough, chills, diarrhea, nausea,
encephalopathy, decreased appetite, upper respiratory tract
infection, headache, tachycardia, dizziness, dyspnea, edema, viral
infections, coagulopathy, constipation, and vomiting.1 The most
common Grade 3 or 4 laboratory adverse reactions (incidence greater
than or equal to 50%) include lymphopenia, neutropenia, white blood
cell decreased, thrombocytopenia, and anemia.1
CARVYKTI® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE
SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT
CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome (CRS),
including fatal or life-threatening reactions, occurred in patients
following treatment with CARVYKTI®. Do not administer CARVYKTI® to
patients with active infection or inflammatory disorders. Treat
severe or life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS), which may be fatal or
life-threatening, occurred following treatment with CARVYKTI®,
including before CRS onset, concurrently with CRS, after CRS
resolution, or in the absence of CRS. Monitor for neurologic events
after treatment with CARVYKTI®. Provide supportive care and/or
corticosteroids as needed.
Parkinsonism and Guillain-Barré
syndrome (GBS) and their associated complications resulting in
fatal or life-threatening reactions have occurred following
treatment with CARVYKTI®.
Hemophagocytic
Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS),
including fatal and life-threatening reactions, occurred in
patients following treatment with CARVYKTI®. HLH/MAS can occur with
CRS or neurologic toxicities
Prolonged and/or recurrent cytopenias
with bleeding and infection and requirement for stem cell
transplantation for hematopoietic recovery occurred following
treatment with CARVYKTI®.
Secondary hematological malignancies,
including myelodysplastic syndrome and acute myeloid leukemia, have
occurred in patients following treatment with CARVYKTI®. T-cell
malignancies have occurred following treatment of hematologic
malignancies with BCMA- and CD19-directed genetically modified
autologous T-cell immunotherapies, including CARVYKTI®.
CARVYKTI® is available only through a
restricted program under a Risk Evaluation and Mitigation Strategy
(REMS) called the CARVYKTI® REMS Program.
WARNINGS AND PRECAUTIONS
INCREASED EARLY MORTALITY - In CARTITUDE-4, a (1:1)
randomized controlled trial, there was a numerically higher
percentage of early deaths in patients randomized to the
CARVYKTI® treatment arm compared to the control arm. Among
patients with deaths occurring within the first 10 months from
randomization, a greater proportion (29/208; 14%) occurred in the
CARVYKTI® arm compared to (25/211; 12%) in the control arm.
Of the 29 deaths that occurred in the CARVYKTI® arm within
the first 10 months of randomization, 10 deaths occurred prior to
CARVYKTI® infusion, and 19 deaths occurred after
CARVYKTI® infusion. Of the 10 deaths that occurred prior to
CARVYKTI® infusion, all occurred due to disease progression,
and none occurred due to adverse events. Of the 19 deaths that
occurred after CARVYKTI® infusion, 3 occurred due to disease
progression, and 16 occurred due to adverse events. The most common
adverse events were due to infection (n=12).
CYTOKINE RELEASE SYNDROME (CRS), including fatal or
life-threatening reactions, occurred following treatment with
CARVYKTI®. Among patients receiving CARVYKTI® for
RRMM in the CARTITUDE-1 & 4 studies (N=285), CRS occurred in
84% (238/285), including ≥ Grade 3 CRS (ASCT 2019) in 4% (11/285)
of patients. Median time to onset of CRS, any grade, was 7 days
(range: 1 to 23 days). CRS resolved in 82% with a median duration
of 4 days (range: 1 to 97 days). The most common manifestations of
CRS in all patients combined (≥ 10%) included fever (84%),
hypotension (29%) and aspartate aminotransferase increased (11%).
Serious events that may be associated with CRS include pyrexia,
hemophagocytic lymphohistiocytosis, respiratory failure,
disseminated intravascular coagulation, capillary leak syndrome,
and supraventricular and ventricular tachycardia. CRS occurred in
78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of
patients in CARTITUDE-1 (4% Grade 3 to 4).
Identify CRS based on clinical presentation. Evaluate for and
treat other causes of fever, hypoxia, and hypotension. CRS has been
reported to be associated with findings of HLH/MAS, and the
physiology of the syndromes may overlap. HLH/MAS is a potentially
life-threatening condition. In patients with progressive symptoms
of CRS or refractory CRS despite treatment, evaluate for evidence
of HLH/MAS. Please see Section 5.4; Hemophagocytic
Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS).
Ensure that a minimum of two doses of tocilizumab are available
prior to infusion of CARVYKTI®.
Of the 285 patients who received CARVYKTI® in clinical
trials, 53% (150/285) patients received tocilizumab; 35% (100/285)
received a single dose, while 18% (50/285) received more than 1
dose of tocilizumab. Overall, 14% (39/285) of patients received at
least one dose of corticosteroids for treatment of CRS.
Monitor patients at least daily for 10 days following
CARVYKTI® infusion at a REMS-certified healthcare facility
for signs and symptoms of CRS. Monitor patients for signs or
symptoms of CRS for at least 4 weeks after infusion. At the first
sign of CRS, immediately institute treatment with supportive care,
tocilizumab, or tocilizumab and corticosteroids.
Counsel patients to seek immediate medical attention should
signs or symptoms of CRS occur at any time.
NEUROLOGIC TOXICITIES, which may be severe,
life-threatening, or fatal, occurred following treatment with
CARVYKTI®. Neurologic toxicities included ICANS, neurologic
toxicity with signs and symptoms of parkinsonism, GBS, immune
mediated myelitis, peripheral neuropathies, and cranial nerve
palsies. Counsel patients on the signs and symptoms of these
neurologic toxicities, and on the delayed nature of onset of some
of these toxicities. Instruct patients to seek immediate medical
attention for further assessment and management if signs or
symptoms of any of these neurologic toxicities occur at any
time.
Among patients receiving CARVYKTI® in the CARTITUDE-1
& 4 studies for RRMM, one or more neurologic toxicities
occurred in 24% (69/285), including ≥ Grade 3 cases in 7% (19/285)
of patients. Median time to onset was 10 days (range: 1 to 101)
with 63/69 (91%) of cases developing by 30 days. Neurologic
toxicities resolved in 72% (50/69) of patients with a median
duration to resolution of 23 days (range: 1 to 544). Of patients
developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes
of neurologic toxicities included ICANS in 13%, peripheral
neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%,
and immune mediated myelitis in 0.4% of the patients.
Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS): Patients receiving
CARVYKTI® may experience fatal or life-threatening ICANS
following treatment with CARVYKTI®, including before CRS
onset, concurrently with CRS, after CRS resolution, or in the
absence of CRS.
Among patients receiving CARVYKTI® in the CARTITUDE-1
& 4 studies, ICANS occurred in 13% (36/285), including Grade ≥3
in 2% (6/285) of the patients. Median time to onset of ICANS was 8
days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of
patients with a median time to resolution of 3 days (range: 1 to
143 days). Median duration of ICANS was 6 days (range: 1 to 1229
days) in all patients including those with ongoing neurologic
events at the time of death or data cut-off. Of patients with
ICANS, 97% (35/36) had CRS. The onset of ICANS occurred during CRS
in 69% of patients, before and after the onset of CRS in 14% of
patients respectively.
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)
occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23%
of patients in CARTITUDE-1 (3% Grade 3). The most frequent ≥2%
manifestations of ICANS included encephalopathy (12%), aphasia
(4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep
disorder (2%) [see Adverse Reactions (6.1)].
Monitor patients at least daily for 10 days following
CARVYKTI® infusion at the REMS-certified healthcare facility
for signs and symptoms of ICANS. Rule out other causes of ICANS
symptoms. Monitor patients for signs or symptoms of ICANS for at
least 4 weeks after infusion and treat promptly. Neurologic
toxicity should be managed with supportive care and/or
corticosteroids as needed [see Dosage and Administration
(2.3)].
Parkinsonism: Neurologic toxicity
with parkinsonism has been reported in clinical trials of
CARVYKTI®. Among patients receiving CARVYKTI® in the
CARTITUDE-1 & 4 studies, parkinsonism occurred in 3% (8/285),
including Grade ≥ 3 in 2% (5/285) of the patients. Median time to
onset of parkinsonism was 56 days (range: 14 to 914 days).
Parkinsonism resolved in 1 of 8 (13%) of patients with a median
time to resolution of 523 days. Median duration of parkinsonism was
243.5 days (range: 62 to 720 days) in all patients including those
with ongoing neurologic events at the time of death or data
cut-off. The onset of parkinsonism occurred after CRS for all
patients and after ICANS for 6 patients.
Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade
3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4).
Manifestations of parkinsonism included movement disorders,
cognitive impairment, and personality changes. Monitor patients for
signs and symptoms of parkinsonism that may be delayed in onset and
managed with supportive care measures. There is limited efficacy
information with medications used for the treatment of Parkinson’s
disease for the improvement or resolution of parkinsonism symptoms
following CARVYKTI® treatment.
Guillain-Barré Syndrome: A fatal
outcome following GBS occurred following treatment with
CARVYKTI® despite treatment with intravenous
immunoglobulins. Symptoms reported include those consistent with
Miller-Fisher variant of GBS, encephalopathy, motor weakness,
speech disturbances, and polyradiculoneuritis.
Monitor for GBS. Evaluate patients presenting with peripheral
neuropathy for GBS. Consider treatment of GBS with supportive care
measures and in conjunction with immunoglobulins and plasma
exchange, depending on severity of GBS.
Immune Mediated Myelitis: Grade 3
myelitis occurred 25 days following treatment with CARVYKTI®
in CARTITUDE-4 in a patient who received CARVYKTI® as
subsequent therapy. Symptoms reported included hypoesthesia of the
lower extremities and the lower abdomen with impaired sphincter
control. Symptoms improved with the use of corticosteroids and
intravenous immune globulin. Myelitis was ongoing at the time of
death from other cause.
Peripheral Neuropathy occurred
following treatment with CARVYKTI®. Among patients receiving
CARVYKTI® in the CARTITUDE-1 & 4 studies, peripheral
neuropathy occurred in 7% (21/285), including Grade ≥3 in 1%
(3/285) of the patients. Median time to onset of peripheral
neuropathy was 57 days (range: 1 to 914 days). Peripheral
neuropathy resolved in 11 of 21 (52%) of patients with a median
time to resolution of 58 days (range: 1 to 215 days). Median
duration of peripheral neuropathy was 149.5 days (range: 1 to 692
days) in all patients including those with ongoing neurologic
events at the time of death or data cut-off.
Peripheral neuropathies occurred in 7% of patients in
CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in
CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and
symptoms of peripheral neuropathies. Patients who experience
peripheral neuropathy may also experience cranial nerve palsies or
GBS.
Cranial Nerve Palsies occurred
following treatment with CARVYKTI®. Among patients receiving
CARVYKTI® in the CARTITUDE-1 & 4 studies, cranial nerve
palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285)
of the patients. Median time to onset of cranial nerve palsies was
21 days (range: 17 to 101 days). Cranial nerve palsies resolved in
17 of 19 (89%) of patients with a median time to resolution of 66
days (range: 1 to 209 days). Median duration of cranial nerve
palsies was 70 days (range: 1 to 262 days) in all patients
including those with ongoing neurologic events at the time of death
or data cut-off. Cranial nerve palsies occurred in 9% of patients
in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in
CARTITUDE-1 (1% Grade 3 to 4).
The most frequent cranial nerve affected was the 7th cranial
nerve. Additionally, cranial nerves III, V, and VI have been
reported to be affected.
Monitor patients for signs and symptoms of cranial nerve
palsies. Consider management with systemic corticosteroids,
depending on the severity and progression of signs and
symptoms.
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)/MACROPHAGE
ACTIVATION SYNDROME (MAS): Among patients receiving
CARVYKTI® in the CARTITUDE-1 & 4 studies, HLH/MAS
occurred in 1% (3/285) of patients. All events of HLH/MAS had onset
within 99 days of receiving CARVYKTI®, with a median onset
of 10 days (range: 8 to 99 days) and all occurred in the setting of
ongoing or worsening CRS. The manifestations of HLH/MAS included
hyperferritinemia, hypotension, hypoxia with diffuse alveolar
damage, coagulopathy and hemorrhage, cytopenia, and multi-organ
dysfunction, including renal dysfunction and respiratory
failure.
Patients who develop HLH/MAS have an increased risk of severe
bleeding. Monitor hematologic parameters in patients with HLH/MAS
and transfuse per institutional guidelines. Fatal cases of HLH/MAS
occurred following treatment with CARVYKTI®.
HLH is a life-threatening condition with a high mortality rate
if not recognized and treated early. Treatment of HLH/MAS should be
administered per institutional standards.
CARVYKTI® REMS: Because of the risk of CRS and neurologic
toxicities, CARVYKTI® is available only through a restricted
program under a Risk Evaluation and Mitigation Strategy (REMS)
called the CARVYKTI® REMS.
Further information is available at https://www.carvyktirems.com
or 1-844-672-0067.
PROLONGED AND RECURRENT CYTOPENIAS: Patients may exhibit
prolonged and recurrent cytopenias following lymphodepleting
chemotherapy and CARVYKTI® infusion.
Among patients receiving CARVYKTI® in the CARTITUDE-1
& 4 studies, Grade 3 or higher cytopenias not resolved by day
30 following CARVYKTI® infusion occurred in 62% (176/285) of
the patients and included thrombocytopenia 33% (94/285),
neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2%
(6/285). After Day 60 following CARVYKTI® infusion 22%, 20%,
5%, and 6% of patients had a recurrence of Grade 3 or 4
lymphopenia, neutropenia, thrombocytopenia, and anemia
respectively, after initial recovery of their Grade 3 or 4
cytopenia. Seventy-seven percent (219/285) of patients had one,
two, or three or more recurrences of Grade 3 or 4 cytopenias after
initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients
had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at
the time of death.
Monitor blood counts prior to and after CARVYKTI®
infusion. Manage cytopenias with growth factors and blood product
transfusion support according to local institutional
guidelines.
INFECTIONS: CARVYKTI® should not be administered
to patients with active infection or inflammatory disorders.
Severe, life-threatening, or fatal infections, occurred in patients
after CARVYKTI® infusion.
Among patients receiving CARVYKTI® in the CARTITUDE-1
& 4 studies, infections occurred in 57% (163/285), including
≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with
an unspecified pathogen occurred in 12%, viral infections in 6%,
bacterial infections in 5%, and fungal infections in 1% of
patients. Overall, 5% (13/285) of patients had Grade 5 infections,
2.5% of which were due to COVID-19. Patients treated with
CARVYKTI® had an increased rate of fatal COVID-19 infections
compared to the standard therapy arm.
Monitor patients for signs and symptoms of infection before and
after CARVYKTI® infusion and treat patients appropriately.
Administer prophylactic, pre-emptive, and/or therapeutic
antimicrobials according to the standard institutional guidelines.
Febrile neutropenia was observed in 5% of patients after
CARVYKTI® 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. Counsel patients on the importance of
prevention measures. Follow institutional guidelines for the
vaccination and management of immunocompromised patients with
COVID-19.
Viral Reactivation: Hepatitis B
virus (HBV) reactivation, in some cases resulting in fulminant
hepatitis, hepatic failure, and death, can occur in patients with
hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV),
HBV, hepatitis C virus (HCV), human immunodeficiency virus (HIV),
or any other infectious agents if clinically indicated in
accordance with clinical guidelines before collection of cells for
manufacturing. Consider antiviral therapy to prevent viral
reactivation per local institutional guidelines/clinical
practice.
HYPOGAMMAGLOBULINEMIA: can occur in patients receiving
treatment with CARVYKTI®. Among patients receiving
CARVYKTI® in the CARTITUDE-1 & 4 studies,
hypogammaglobulinemia adverse event was reported in 36% (102/285)
of patients; laboratory IgG levels fell below 500mg/dl after
infusion in 93% (265/285) of patients. Hypogammaglobulinemia either
as an adverse reaction or laboratory IgG level below 500mg/dl,
after infusion occurred in 94% (267/285) of patients treated.
Fifty-six percent (161/285) of patients received intravenous
immunoglobulin (IVIG) post CARVYKTI® for either an adverse
reaction or prophylaxis.
Monitor immunoglobulin levels after treatment with
CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage
per local institutional guidelines, including infection precautions
and antibiotic or antiviral prophylaxis.
Use of Live Vaccines: The safety of
immunization with live viral vaccines during or following
CARVYKTI® 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
CARVYKTI® treatment, and until immune recovery following
treatment with CARVYKTI®.
HYPERSENSITIVITY REACTIONS occurred following treatment
with CARVYKTI®. Among patients receiving CARVYKTI® in
the CARTITUDE-1 & 4 studies, hypersensitivity reactions
occurred in 5% (13/285), all of which were ≤ Grade 2.
Manifestations of hypersensitivity reactions included flushing,
chest discomfort, tachycardia, wheezing, tremor, burning sensation,
non-cardiac chest pain, and pyrexia.
Serious hypersensitivity reactions, including anaphylaxis, may
be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®.
Patients should be carefully monitored for 2 hours after infusion
for signs and symptoms of severe reaction. Treat promptly and
manage patients appropriately according to the severity of the
hypersensitivity reaction.
SECONDARY MALIGNANCIES: Patients treated with
CARVYKTI® may develop secondary malignancies. Among patients
receiving CARVYKTI® in the CARTITUDE-1 & 4 studies,
myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of
myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1
case of myelodysplastic syndrome followed by acute myeloid
leukemia). The median time to onset of myeloid neoplasms was 447
days (range: 56 to 870 days) after treatment with CARVYKTI®.
Ten of these 13 patients died following the development of myeloid
neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after
initiation of subsequent antimyeloma therapy. Cases of
myelodysplastic syndrome and acute myeloid leukemia have also been
reported in the post-marketing setting. T-cell malignancies have
occurred following treatment of hematologic malignancies with BCMA-
and CD19-directed genetically modified autologous T-cell
immunotherapies, including CARVYKTI®. Mature T-cell
malignancies, including CAR-positive tumors, may present as soon as
weeks following infusions and may include fatal outcomes.
Monitor life-long for secondary malignancies. In the event that
a secondary malignancy occurs, contact Janssen Biotech, Inc. at
1-800-526-7736 for reporting and to obtain instructions on
collection of patient samples.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the
potential for neurologic events, including altered mental status,
seizures, neurocognitive decline, or neuropathy, patients receiving
CARVYKTI® are at risk for altered or decreased consciousness
or coordination in the 8 weeks following CARVYKTI® 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, and in the event of
new onset of any neurologic toxicities.
ADVERSE REACTIONS
The most common nonlaboratory adverse reactions (incidence
greater than 20%) are pyrexia, cytokine release syndrome,
hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue,
infections-pathogen unspecified, cough, chills, diarrhea, nausea,
encephalopathy, decreased appetite, upper respiratory tract
infection, headache, tachycardia, dizziness, dyspnea, edema, viral
infections, coagulopathy, constipation, and vomiting. The most
common Grade 3 or 4 laboratory adverse reactions (incidence greater
than or equal to 50%) include lymphopenia, neutropenia, white blood
cell decreased, thrombocytopenia, and anemia.
Please read full Prescribing Information, including Boxed
Warning, for CARVYKTI®.
ABOUT CARVYKTI® (CILTACABTAGENE AUTOLEUCEL;
CILTA-CEL)
Ciltacabtagene autoleucel is a BCMA-directed, genetically
modified autologous T-cell immunotherapy, which involves
reprogramming a patient’s own T-cells with a transgene encoding a
chimeric antigen receptor (CAR) that identifies and eliminates
cells that express BCMA. The cilta-cel CAR protein features two
BCMA-targeting single domain antibodies designed to confer high
avidity against human BCMA. Upon binding to BCMA-expressing cells,
the CAR promotes T-cell activation, expansion, and elimination of
target cells.1
In December 2017, Legend Biotech entered into an exclusive
worldwide license and collaboration agreement with Janssen Biotech,
Inc. (Janssen), a Johnson & Johnson company, to develop and
commercialize cilta-cel. In February 2022, cilta-cel was approved
by the U.S. Food and Drug Administration (FDA) under the brand name
CARVYKTI® for the treatment of adults with relapsed or refractory
multiple myeloma. In May 2022, the European Commission (EC) granted
conditional marketing authorization of CARVYKTI® for the treatment
of adults with relapsed and refractory multiple myeloma. In
September 2022, Japan’s Ministry of Health, Labour and Welfare
(MHLW) approved CARVYKTI®. Cilta-cel was granted Breakthrough
Therapy Designation in the U.S. in December 2019 and in China in
August 2020. In addition, cilta-cel received a PRIority MEdicines
(PRIME) designation from the European Commission in April 2019.
Cilta-cel also received Orphan Drug Designation from the U.S. FDA
in February 2019, from the European Commission in February 2020,
and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in
Japan in June 2020. In March 2022, the European Medicines Agency’s
Committee for Orphan Medicinal Products recommended by consensus
that the orphan designation for cilta-cel be maintained on the
basis of clinical data demonstrating improved and sustained
complete response rates following treatment.
ABOUT CARTITUDE-4
CARTITUDE-4 (NCT04181827) is an ongoing, international,
randomized, open-label Phase 3 study evaluating the efficacy and
safety of cilta-cel versus pomalidomide, bortezomib and
dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone
(DPd) in adult patients with relapsed and lenalidomide-refractory
multiple myeloma who received one to three prior lines of therapy,
including a PI and an IMiD. The primary endpoint of the study was
progression-free survival.2
ABOUT MULTIPLE MYELOMA
Multiple myeloma is an incurable blood cancer that starts in the
bone marrow and is characterized by an excessive proliferation of
plasma cells.3 In 2024, it is estimated that more than 35,000
people will be diagnosed with multiple myeloma, and more than
12,000 people will die from the disease in the U.S.4 While some
patients with multiple myeloma initially have no symptoms, most
patients are diagnosed due to symptoms that can include bone
problems, low blood counts, calcium elevation, kidney problems or
infections.5
ABOUT LEGEND BIOTECH
Legend Biotech is a global biotechnology company dedicated to
treating, and one day curing, life-threatening diseases.
Headquartered in Somerset, New Jersey, we are developing advanced
cell therapies across a diverse array of technology platforms,
including autologous and allogeneic chimeric antigen receptor
T-cell, gamma-delta T cell (gd T) and natural killer (NK)
cell-based immunotherapy. From our three R&D sites around the
world, we apply these innovative technologies to pursue the
discovery of cutting-edge therapeutics for patients worldwide.
Learn more at www.legendbiotech.com and follow us on X (formerly
Twitter) and LinkedIn.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Statements in this press release about future expectations,
plans, and prospects, as well as any other statements regarding
matters that are not historical facts, constitute “forward-looking
statements” within the meaning of The Private Securities Litigation
Reform Act of 1995. These statements include, but are not limited
to, statements relating to Legend Biotech’s strategies and
objectives; statements relating to CARVYKTI®, including Legend
Biotech’s expectations for CARVYKTI® and its therapeutic potential;
statements relating to the potential approval of CARVYKTI® for
earlier lines of therapy; statements related to Legend Biotech
manufacturing expectations for CARVYKTI®; and the potential
benefits of Legend Biotech’s product candidates. The words
“anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,”
“intend,” “may,” “plan,” “potential,” “predict,” “project,”
“should,” “target,” “will,” “would” and similar expressions are
intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Actual
results may differ materially from those indicated by such
forward-looking statements as a result of various important
factors. Legend Biotech’s expectations could be affected by, among
other things, uncertainties involved in the development of new
pharmaceutical products; unexpected clinical trial results,
including as a result of additional analysis of existing clinical
data or unexpected new clinical data; unexpected regulatory actions
or delays, including requests for additional safety and/or efficacy
data or analysis of data, or government regulation generally;
unexpected delays as a result of actions undertaken, or failures to
act, by our third party partners; uncertainties arising from
challenges to Legend Biotech’s patent or other proprietary
intellectual property protection, including the uncertainties
involved in the U.S. litigation process; government, industry, and
general product pricing and other political pressures; as well as
the other factors discussed in the “Risk Factors” section of Legend
Biotech’s Annual Report on Form 20-F filed with the Securities and
Exchange Commission on March19, 2024. Should one or more of these
risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially
from those described in this press release as anticipated,
believed, estimated or expected. Any forward-looking statements
contained in this press release speak only as of the date of this
press release. Legend Biotech specifically disclaims any obligation
to update any forward-looking statement, whether as a result of new
information, future events or otherwise.
†Surbhi Sidana, M.D., Assistant Professor of Medicine, Blood and
Marrow Transplantation & Cellular Therapy at Stanford
University School of Medicine has provided consulting and advisory
services to Legend Biotech; she has not been paid for any media
work.
REFERENCES
___________________________ 1 CARVYKTI Prescribing
Information. Horsham, PA: Janssen Biotech, Inc. 2
ClinicalTrials.Gov. A Study Comparing JNJ-68284528, a CAR-T Therapy
Directed Against B-cell Maturation Antigen (BCMA), Versus
Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab,
Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed
and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4).
https://www.clinicaltrials.gov/study/NCT04181827. Accessed March
2024. 3 American Cancer Society. ”What is Multiple Myeloma?”.
Available at:
https://www.cancer.org/cancer/types/multiple-myeloma/about/what-is-multiple-myeloma.html.
Accessed March 2024. 4 American Cancer Society. “Key Statistics
About Multiple Myeloma.” Available at:
https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statistics.html.
Accessed March 2024. 5 American Cancer Society. Multiple myeloma:
early detection, diagnosis, and staging. Available at:
https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf.
Accessed March 2023.
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INVESTOR CONTACT: Jessie Yeung Tel: (732) 956-8271
jessie.yeung@legendbiotech.com PRESS CONTACT: Mary Ann
Ondish Tel: (914) 552-4625 media@legendbiotech.com
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