- Eight presentations at ASCO and EHA 2023 Annual Meetings
showcase continued leadership in CAR-T cell therapy research for
patients with multiple myeloma across various clinical
settings
- First analysis from the CARTITUDE-4 Phase 3 study in relapsed
and lenalidomide-refractory multiple myeloma patients with one to
three earlier lines of therapy to be presented as an oral
presentation at ASCO and in a plenary session at EHA
- Data from the final analysis of the CARTITUDE-1 study
Legend Biotech Corporation (“Legend Biotech” or the “Company”)
(NASDAQ: LEGN), a global biotechnology company developing,
manufacturing and commercializing novel therapies to treat
life-threatening diseases, today announced that new and updated
data from the CARTITUDE Clinical Development Program evaluating
ciltacabtagene autoleucel (cilta-cel) will be presented at the 2023
American Society of Clinical Oncology (ASCO) Annual Meeting and the
European Hematology Association’s (EHA) 2023 Hybrid Congress.
Five-year follow-up data from Legend-2 (NCT03090659), an
investigator-initiated trial that has been assessing a similar CAR
construct since 2015, will also be presented at the meetings.
From the CARTITUDE Clinical Development Program, the first
analysis of the Phase 3 CARTITUDE-4 study was accepted as a late
breaking abstract at ASCO and will be presented as an oral
presentation at both ASCO and in a plenary session at EHA.
CARTITUDE-4 (NCT04181827) is the first international, randomized,
open-label Phase 3 study investigating the treatment of adult
patients with relapsed and lenalidomide-refractory multiple myeloma
who have received cilta-cel vs standard-of-care regimens, including
pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab,
pomalidomide and dexamethasone (DPd), following one to three prior
lines of therapy.
“We are pleased that the latest data from the CARTITUDE-4 study
will be officially presented at the meetings. We are continuing to
investigate cilta-cel in earlier lines of treatment and the readout
from this study is crucial to how we move forward,” said Ying
Huang, Ph.D., Chief Executive Officer of Legend Biotech. “We also
eagerly anticipate the presentation of the five-year follow-up data
from Legend-2 at ASCO. This was the study that showed — in front of
the international community back in 2017 —promising results in
heavily pretreated patients with multiple myeloma. Since then, we
have taken significant steps toward advancing the treatment
landscape for myeloma patients in the CARTITUDE Development Program
and are exploring the potential of other agents in our pipeline for
this and other indications.”
Additional data at this year’s meetings will include longer-term
results from the final protocol-specified analysis of the
CARTITUDE-1 study (NCT03548207), which will be shared as a poster
presentation at ASCO and an oral presentation at EHA. CARTITUDE-1
is a Phase 1b/2 study evaluating cilta-cel for the treatment of
heavily pretreated patients with relapsed or refractory multiple
myeloma. The study’s 18-month follow-up data supported the U.S.
Food and Drug Administration (FDA) approval of CARVYKTI®
(ciltacabtagene autoleucel; cilta-cel) in February 2022.
Data from the 5-year follow-up analysis of LEGEND-2 will be
presented as a poster at ASCO and EHA. This first-in-human, Phase 1
study evaluates LCAR-B38M CAR-T cells in patients with relapsed and
refractory multiple myeloma. It is the longest follow-up for any
BCMA-targeted CAR-T cell therapy study to be presented at the
meetings.
A select list of abstracts from the meetings can be found
below.
ASCO Presentations (June 2-6, 2023)
Abstract Number
Title
Information
Abstract #106
Oral Presentation
First Phase 3 results from CARTITUDE-4:
Cilta-cel versus standard of care (PVd or DPd) in
lenalidomide-refractory multiple myeloma
Session Title: Clinical Science
Symposium – Moving Cellular Therapy into Earlier Lines of Treatment
in Hematologic Malignancies: Latest Efficacy Data and The Need to
Improve Access
Date/Time: June 5, 2023, 9:45 am –
11:15 am CDT
Location: Hall D1 & On
Demand
Abstract #8009
Poster Discussion
CARTITUDE-1 final results: Phase 1b/2
study of ciltacabtagene autoleucel in heavily pretreated patients
with relapsed/refractory multiple myeloma
Session Title: Hematologic
Malignancies – Plasma Cell Dyscrasia
Date/Time: June 5, 2023, 8:00 am –
11:00 am CDT (poster), 3:00 pm – 4:30 pm (discussion)
Location: Hall A & On
Demand
Abstract #8010
Poster Discussion
Long-term remission and survival in
patients with relapsed or refractory multiple myeloma after
treatment of LCAR-B38M CAR-T – at least 5-year follow-up in
LEGEND-2
Session Title: Hematologic
Malignancies – Plasma Cell Dyscrasia
Date/Time: June 5, 2023, 8:00 am –
11:00 am CDT (poster), 3:00 pm – 4:30 pm (discussion)
Location: Hall A & On
Demand
EHA Presentations (June 8-11, 2023)
Abstract Number
Title
Information
Abstract #P904
Poster Presentation
LocoMMotion: A prospective, observational,
multinational study of real-life current standards of care in
patients with relapsed/refractory multiple myeloma – final analysis
at 2-year follow-up
Friday June 9, 2023
18:00 – 19:00 CEST
Abstract #S100
Plenary Session
Encore: First Phase 3 results from
CARTITUDE-4: cilta-cel versus standard of care (PVd or DPd) in
lenalidomide-refractory multiple myeloma
Saturday June 10, 2023
14:45-15:00 CEST
Abstract #S202
Oral Presentation
Encore: CARTITUDE-1 final results:
Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated
patients with relapsed/refractory multiple myeloma
Sunday, June 11, 2023
12:00 –12:15 CEST
Abstract #P874
Poster Presentation
Encore: Long-term remission and
survival in patients with relapsed or refractory multiple myeloma
after treatment of LCAR-B38M CAR-T – at least 5-year follow-up in
LEGEND-2
Friday June 9, 2023
18:00 – 19:00 CEST
Abstract #P922
Poster Presentation
Adjusted comparisons of ciltacabtagene
autoleucel with therapies from real-world clinical practice:
two-year follow-up analysis from CARTITUDE-1 and the prospective
LocoMMotion study
Friday, June 9, 2023
18:00 – 19:00 CEST
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. BCMA is primarily expressed on the surface
of malignant multiple myeloma B-lineage cells, as well as
late-stage B-cells and plasma cells. 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) 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.2
In May 2022, the European Commission (EC) granted conditional
marketing authorization of CARVYKTI® for the treatment of adults
with relapsed and refractory multiple myeloma.3 In September 2022,
Japan’s Ministry of Health, Labour and Welfare (MHLW) approved
CARVYKTI®.4 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.5
ABOUT CARTITUDE-1
CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, single
arm, multi-center trial evaluating cilta-cel for the treatment of
adult patients with relapsed or refractory multiple myeloma, who
previously received at least three prior lines of therapy including
a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and
an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in
the trial, 99 percent were refractory to the last line of treatment
and 88 percent were triple-class refractory, meaning their cancer
did not respond, or no longer responds, to an IMiD, a PI and an
anti-CD38 monoclonal antibody.
ABOUT CARTITUDE-4
CARTITUDE-4 (NCT04181827) is the first 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.
ABOUT LEGEND-2
LEGEND-2 (NCT03090659) is a single arm, open-label,
multi-center, Phase 1/2 study, to determine the safety and efficacy
of LCAR-B38M CAR-T cells in treating patients diagnosed with
refractory/relapsed multiple myeloma.
ABOUT LOCOMMOTION
LocoMMotion (NCT04035226) is a prospective, multinational,
observational study of real-life current standards of care in
patients with relapsed and/or refractory multiple myeloma who
received at least 3 prior lines of therapy including a PI, IMiD and
CD38 monoclonal antibody treatment.
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.6 In 2023, 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.7 While some
patients with multiple myeloma have no symptoms at all, most
patients are diagnosed due to symptoms that can include bone
problems, low blood counts, calcium elevation, kidney problems or
infections.8 Although treatment may result in remission,
unfortunately, patients will most likely relapse.9 Patients who
relapse after treatment with standard therapies, including protease
inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal
antibody, have poor prognoses and few treatment options
available.10,11
CARVYKTI® INDICATIONS AND USAGE
CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation
antigen (BCMA)-directed genetically modified autologous T cell
immunotherapy indicated for the treatment of adult patients with
relapsed or refractory multiple myeloma, after four or more prior
lines of therapy, including a proteasome inhibitor, an
immunomodulatory agent, and an anti-CD38 monoclonal antibody.
CARVYKTI® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME,
NEUROLOGIC TOXICITIES, HLH/MAS, and PROLONGED and RECURRENT
CYTOPENIA
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 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®.
CARVYKTI® is available only through a
restricted program under a Risk Evaluation and Mitigation Strategy
(REMS) called the CARVYKTI® REMS Program.
WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred following treatment with
CARVYKTI® in 95% (92/97) of patients receiving ciltacabtagene
autoleucel. Grade 3 or higher CRS (2019 ASTCT grade) occurred in 5%
(5/97) of patients, with Grade 5 CRS reported in 1 patient. The
median time to onset of CRS was 7 days (range: 112 days). The most
common manifestations of CRS included pyrexia (100%), hypotension
(43%), increased aspartate aminotransferase (AST) (22%), chills
(15%), increased alanine aminotransferase (ALT) (14%) and sinus
tachycardia (11%). Grade 3 or higher events associated with CRS
included increased AST and ALT, hyperbilirubinemia, hypotension,
pyrexia, hypoxia, respiratory failure, acute kidney injury,
disseminated intravascular coagulation and hemorrhage, HLH/MAS,
angina pectoris, supraventricular and ventricular tachycardia,
malaise, myalgias, increased Creactive protein, ferritin, blood
alkaline phosphatase and gamma-glutamyl transferase.
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. One patient with CRS and suspected HLH/MAS developed a
fatal retroperitoneal hemorrhage in the setting of
thrombocytopenia, coagulopathy and anticoagulation.
Sixty-nine of 97 (71%) patients received tocilizumab and/or a
corticosteroid for CRS after infusion of ciltacabtagene autoleucel.
Forty-four (45%) patients received only tocilizumab, of whom 33
(34%) received a single dose and 11 (11%) received more than one
dose; 24 patients (25%) received tocilizumab and a corticosteroid,
and one patient (1%) received only corticosteroids. Ensure that a
minimum of two doses of tocilizumab are available prior to infusion
of CARVYKTI®.
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, Guillain-Barré
Syndrome, 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.
Overall, one or more subtypes of neurologic toxicity described
below occurred following ciltacabtagene autoleucel in 26% (25/97)
of patients, of which 11% (11/97) of patients experienced Grade 3
or higher events. These subtypes of neurologic toxicities were also
observed in two ongoing studies.
Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS): Patients 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. ICANS occurred in 23% (22/97)
of patients receiving ciltacabtagene autoleucel including Grade 3
or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97).
The median time to onset of ICANS was 8 days (range 1-28 days). All
22 patients with ICANS had CRS. The most frequent (≥5%)
manifestation of ICANS included encephalopathy (23%), aphasia (8%)
and headache (6%).
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.
Parkinsonism: Of the 25 patients in
the CARTITUDE-1 study experiencing any neurotoxicity, five male
patients had neurologic toxicity with several signs and symptoms of
parkinsonism, distinct from immune effector cell-associated
neurotoxicity syndrome (ICANS). Neurologic toxicity with
parkinsonism has been reported in other ongoing trials of
ciltacabtagene autoleucel. Patients had parkinsonian and
non-parkinsonian symptoms that included tremor, bradykinesia,
involuntary movements, stereotypy, loss of spontaneous movements,
masked facies, apathy, flat affect, fatigue, rigidity, psychomotor
retardation, micrographia, dysgraphia, apraxia, lethargy,
confusion, somnolence, loss of consciousness, delayed reflexes,
hyperreflexia, memory loss, difficulty swallowing, bowel
incontinence, falls, stooped posture, shuffling gait, muscle
weakness and wasting, motor dysfunction, motor and sensory loss,
akinetic mutism, and frontal lobe release signs. The median onset
of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range
15-108) from infusion of ciltacabtagene autoleucel.
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 Guillain-Barré Syndrome (GBS) has occurred in
another ongoing study of ciltacabtagene autoleucel 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 has occurred 25 days following treatment in another
ongoing study. 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: Six patients
in CARTITUDE-1 developed peripheral neuropathy. These neuropathies
presented as sensory, motor or sensorimotor neuropathies. Median
time of onset of symptoms was 62 days (range 4-136 days), median
duration of peripheral neuropathies was 256 days (range 2-465 days)
including those with ongoing neuropathy. Patients who experienced
peripheral neuropathy also experienced cranial nerve palsies or GBS
in other ongoing trials of ciltacabtagene autoleucel. Monitor
patients for signs and symptoms of peripheral neuropathies.
Cranial Nerve Palsies: Three
patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1.
All three patients had 7th cranial nerve palsy; one patient had 5th
cranial nerve palsy as well. Median time to onset was 26 days
(range 21-101 days) following infusion of ciltacabtagene
autoleucel. Occurrence of 3rd and 6th cranial nerve palsy,
bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy
after improvement, and occurrence of peripheral neuropathy in
patients with cranial nerve palsy have also been reported in
ongoing trials of ciltacabtagene autoleucel. 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): Fatal HLH occurred in one patient
(1%), 99 days after ciltacabtagene autoleucel. The HLH event was
preceded by prolonged CRS lasting 97 days. The manifestations of
HLH/MAS include hypotension, hypoxia with diffuse alveolar damage,
coagulopathy, cytopenia, and multi-organ dysfunction, including
renal dysfunction.
One patient with grade 4 HLH/MAS developed fatal intracerebral
and gastrointestinal hemorrhage in the setting of coagulopathy and
thrombocytopenia 12 days after treatment in another ongoing study.
Patients who develop HLH/MAS have an increased risk of severe
bleeding. Monitor hematological parameters in patients with HLH/MAS
and transfuse per institutional guidelines.
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. One patient underwent
autologous stem cell therapy for hematopoietic reconstitution due
to prolonged thrombocytopenia.
In CARTITUDE-1, 30% (29/97) of patients experienced prolonged
Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced
prolonged Grade 3 or 4 thrombocytopenia that had not resolved by
Day 30 following ciltacabtagene autoleucel infusion.
Recurrent Grade 3 or 4 neutropenia, thrombocytopenia,
lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60%
(58/97), and 37% (36/97) after recovery from initial Grade 3 or 4
cytopenia following infusion. After Day 60 following ciltacabtagene
autoleucel infusion, 31%, 12% and 6% of patients had a recurrence
of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia,
respectively, after initial recovery of their Grade 3 or 4
cytopenia. Eighty-seven percent (84/97) 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. Six and 11 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.
Infections (all grades) occurred in 57 (59%) patients. Grade 3
or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4
infections with an unspecified pathogen occurred in 17%, viral
infections in 7%, bacterial infections in 1%, and fungal infections
in 1% of patients. Overall, four patients had Grade 5 infections:
lung abscess (n=1), sepsis (n=2) and pneumonia (n=1).
Grade 5 infections reported in other studies include
bronchopulmonary aspergillosis, pneumocystis jirovecii pneumonia,
and CMV colitis (with HSV-1 hepatitis). Another patient developed
mycotic aneurysm due to cerebral aspergillosis and died of
subarachnoid hemorrhage.
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 10% of patients after
ciltacabtagene autoleucel 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.
In a randomized controlled study of relapsed or refractory
multiple myeloma (CARTITUDE- 4), patients treated with
ciltacabtagene autoleucel had an increased rate of fatal COVID19
infections compared to the standard therapy arm. 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), and 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 was reported as an adverse event in
12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL
after infusion in 92% (89/97) of patients. 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 have occurred in 5% (5/97) of
patients following ciltacabtagene autoleucel infusion. 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
appropriately according to the severity of the hypersensitivity
reaction.
Secondary Malignancies: Patients may develop secondary
malignancies. 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 for testing of secondary malignancy
of T cell origin.
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 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 non-laboratory adverse reactions (incidence
greater than 20%) are pyrexia, cytokine release syndrome,
hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue,
infections of unspecified pathogen, 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 laboratory adverse reactions (incidence greater than or
equal to 50%) include thrombocytopenia, neutropenia, anemia,
aminotransferase elevation and hypoalbuminemia.
Please read full Prescribing Information including Boxed Warning
for CARVYKTI®.
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 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® and any other product
candidates, including Legend Biotech’s expectations for CARVYKTI®
and any other product candidates, such as Legend Biotech’s
manufacturing and commercialization expectations for CARVYKTI® and
the potential effect of treatment with CARVYKTI® and any other
product candidates; statements about submissions for CARVYKTI® and
any other product candidates, and the progress of such submissions
with the U.S. Food and Drug Administration (FDA) and other
regulatory authorities; the anticipated timing of, and ability to
progress, clinical trials; the ability to generate, analyze and
present data from clinical trials; expected results of clinical
trials; 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; competition
in general; government, industry, and general product pricing and
other political pressures; the duration and severity of the
COVID-19 pandemic and governmental and regulatory measures
implemented in response to the evolving situation; 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 March 30, 2023. 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.
____________________________ 1 CARVYKTI™ Prescribing
Information. Horsham, PA: Janssen Biotech, Inc. 2 CARVYKTI™
(ciltacabtagene autoleucel), BCMA-Directed CAR-T Therapy, Receives
U.S. FDA Approval for the Treatment of Adult Patients with Relapsed
or Refractory Multiple Myeloma. Available at:
https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-bcma-directed-car-t-therapy-receives-u-s-fda-approval-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-multiple-myeloma/.
Accessed April 2023. 3 CARVYKTI (ciltacabtagene autoleucel) Granted
Conditional Approval by the European Commission for the Treatment
of Patients with Relapsed and Refractory Multiple Myeloma.
Available at:
https://legendbiotech.com/legend-news/carvykti-ciltacabtagene-autoleucel-granted-conditional-approval-by-the-european-commission-for-the-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma/.
Accessed April 2023. 4 CARVYKTI™ (ciltacabtagene autoleucel)
Receives Approval from Japan’s Ministry of Health, Labour and
Welfare (MHLW) for the Treatment of Patients with Relapsed or
Refractory Multiple Myeloma. Available at:
https://www.businesswire.com/news/home/20220926005847/en/CARVYKTI%E2%84%A2-ciltacabtagene-autoleucel-Receives-Approval-from-Japan%E2%80%99s-Ministry-of-Health-Labour-and-Welfare-MHLW-for-the-Treatment-of-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma.
Accessed April 2023. 5 European Commission. Community Register of
Orphan Medicinal Products. Available at:
https://ec.europa.eu/health/documents/community-register/html/o2252.htm.
Accessed April 2023. 6 American Society of Clinical Oncology.
Multiple myeloma: introduction. https://www.cancer.net/cancer-
types/multiple-myeloma/introduction. Accessed March 2023. 7
American Cancer Society. “Key Statistics About Multiple Myeloma.”
Available at:
https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370%20in%20women).
Accessed April 2023. 8 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 April 2023. 9 Rajkumar SV. Multiple myeloma: 2020 update
on diagnosis, risk-stratification and management. Am J Hematol.
2020;95(5),548-567. doi:10.1002/ajh.25791. 10 Kumar SK, Dimopoulos
MA, Kastritis E, et al. Natural history of relapsed myeloma,
refractory to immunomodulatory drugs and proteasome inhibitors: a
multicenter IMWG study. Leukemia. 2017;31(11):2443- 2448. 11 Gandhi
UH, Cornell RF, Lakshman A, et al. Outcomes of patients with
multiple myeloma refractory to CD38- targeted monoclonal antibody
therapy. Leukemia. 2019;33(9):2266-2275.
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version on businesswire.com: https://www.businesswire.com/news/home/20230516005654/en/
PRESS CONTACT: Tina Carter, Corporate Communications
Lead, Legend Biotech tina.carter@legendbiotech.com (908)
331-5025
INVESTOR CONTACTS: Joanne Choi, Senior Manager, Investor
Relations, Legend Biotech joanne.choi@legendbiotech.com
Crystal Chen, Manager, Investor Relations, Legend Biotech
crystal.chen@legendbiotech.cn
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