- TEPKINLY® (epcoritamab) is the first and only
subcutaneous bispecific antibody approved as a monotherapy for
adult patients with relapsed or refractory diffuse large B-cell
lymphoma after two or more lines of systemic therapy
- Conditional marketing authorization approval from the
European Commission is supported by data from the pivotal Phase 1/2
EPCORE™ NHL-1 clinical trial
- TEPKINLY represents AbbVie's second approved hematological
cancer treatment in the European Union
NORTH
CHICAGO, Ill., Sept. 25,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that the European Commission (EC) has granted conditional
marketing authorization for TEPKINLY® (epcoritamab) as a
monotherapy for the treatment of adult patients with relapsed or
refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or
more lines of systemic therapy. TEPKINLY is the first and only
subcutaneous T-cell engaging bispecific antibody approved for the
treatment of this patient population in the European Union
(EU), as well as Liechtenstein, Norway and Iceland.
DLBCL is the most common type of B-cell non-Hodgkin's lymphoma
worldwide.1 While patients may have access to
chemoimmunotherapy regimens to treat their disease, they face
limited treatment options, with few readily available,
off-the-shelf medicines, especially for those whose disease has
relapsed or become refractory to prior treatments.1
"The European Commission approval of epcoritamab represents a
significant milestone in our aspiration with Genmab to develop a
potential core therapy for patients with B-cell malignancies, like
DLBCL," said Roopal Thakkar, senior
vice president, development and regulatory affairs, chief medical
officer, AbbVie. "With this milestone achievement, TEPKINLY is now
the second approved cancer treatment in the EU from our oncology
portfolio, and AbbVie's third blood cancer medicine across the
world. We remain committed to developing new innovative medicines
that help improve the lives of people with hematological
cancers."
This conditional approval is supported by data from the pivotal
EPCORE™ NHL-1 Phase 1/2 open-label, multi-cohort, multi-center,
single-arm trial evaluating the preliminary efficacy and safety of
TEPKINLY in patients with R/R large B-cell lymphoma (LBCL),
including its subtype DLBCL. In this study, DLBCL patients treated
with TEPKINLY (N=139) achieved an overall response rate of 62
percent and a complete response rate of 39 percent. The median
duration of response was 15.5 months (range: 9.7, not reached).
Results from the trial showed that TEPKINLY demonstrated a
manageable safety profile across the LBCL patient cohort (N=167),
which included the DLBCL patient population. The most common
adverse reactions (≥ 20 percent) were cytokine release syndrome,
fatigue, neutropenia, injection site reaction, musculoskeletal
pain, abdominal pain, pyrexia, nausea and diarrhea.
"Relapsed or refractory DLBCL is an aggressive cancer and
patients can face a difficult and emotional treatment journey. At
this point in the journey, a patient may have had multiple lines of
therapy and will already have experienced relapse," said Anna
Sureda, M.D., Ph.D., head of clinical hematology department,
Institut Català d'Oncologia – L'Hospitalet, Barcelona, Spain. "This European
Commission approval represents an important moment for the DLBCL
patient community and brings with it a potential opportunity for
effective disease management for a condition with limited available
treatment options."
Conditional marketing authorization is granted to medicines that
address an unmet medical need, where the benefit of its immediate
availability to patients outweighs the risk of limited data
availability, and where comprehensive data will be
provided.2
TEPKINLY is being co-developed by AbbVie and Genmab as part of
the companies' oncology collaboration. The companies will share
commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further
global commercialization. AbbVie will continue to pursue regulatory
submissions for epcoritamab across international markets throughout
the year.
About the EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 evaluated epcoritamab as a monotherapy in patients
with CD20+ relapsed or refractory (R/R) large B-cell lymphoma
(LBCL), including diffuse large B-cell lymphoma (DLBCL), after two
or more lines of systemic therapy.3 The study included a
dose escalation part and an expansion part.3 The primary
efficacy endpoint was overall response rate determined by Lugano
criteria (2014) as assessed by an independent review
committee.3 More information can be found on
www.clinicaltrials.gov.
About TEPKINLY® (epcoritamab)
TEPKINLY is
an investigational IgG1-bispecific antibody created using Genmab's
proprietary DuoBody® technology. Genmab's
DuoBody®-CD3 technology is designed to direct cytotoxic
T-cells selectively to elicit an immune response toward target cell
types. TEPKINLY is designed to simultaneously bind to CD3 on
T-cells and CD20 on B-cells and induces T-cell mediated killing of
CD20+ cells.4 CD20 is expressed on B-cells and is a
clinically validated therapeutic target in many B-cell
malignancies, including DLBCL, follicular lymphoma, mantle cell
lymphoma and chronic lymphocytic leukemia.5,6
The U.S. Food and Drug Administration (FDA) approved epcoritamab
under the brand name EPKINLY™ (epcoritamab-bysp) in May 2023 for the treatment of adult patients with
R/R DLBCL, not otherwise specified, including DLBCL arising from
indolent lymphoma, and high-grade B-cell lymphoma, after two or
more lines of systemic therapy. EPKINLY is approved under the FDA's
Accelerated Approval program based on response rate and durability
of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials.
EU Indications and Important Safety Information about
Tepkinly® ▼ (epcoritamab)
Indications
Tepkinly (epcoritamab) as
monotherapy is indicated for the treatment of adult patients with
relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after
two or more lines of systemic therapy.
Important Safety Information
Contraindications
Hypersensitivity to the active
substance or to any of the excipients.
Special warnings and precautions for use
Cytokine
release syndrome (CRS)
CRS, which may be life-threatening or fatal, occurred in patients
receiving Tepkinly. The most common signs and symptoms of CRS
include pyrexia, hypotension and hypoxia. Other signs and symptoms
of CRS in more than two patients include chills, tachycardia,
headache and dyspnoea.
Most CRS events occurred in Cycle 1 and were associated with the
first full dose of Tepkinly. Administer prophylactic
corticosteroids to mitigate the risk of CRS. Patients should be
monitored for signs and symptoms of CRS following Tepkinly
administration. Patients should be hospitalised for 24 hours after
administration of the Cycle 1 Day 15 dose of 48 mg to monitor for
signs and symptoms of CRS. At the first signs or symptoms
of CRS, institute treatment of supportive care with
tocilizumab and/or corticosteroids as appropriate. Patients should
be counselled on the signs and symptoms associated with CRS and
patients should be instructed to contact their healthcare
professional and seek immediate medical attention should signs or
symptoms occur at any time. Management of CRS may require either
temporary delay or discontinuation of Tepkinly based on the
severity of CRS.
Immune effector cell-associated neurotoxicity syndrome
(ICANS)
ICANS, including a fatal event, have occurred in patients receiving
Tepkinly. ICANS may manifest as aphasia, altered level of
consciousness, impairment of cognitive skills, motor weakness,
seizures, and cerebral oedema. The majority of cases of ICANS
occurred within Cycle 1 of Tepkinly treatment, however some
occurred with delayed onset. Patients should be monitored for signs
and symptoms of ICANS following Tepkinly administration. Patients
should be hospitalised for 24 hours after administration of the
Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of
ICANS. At the first signs or symptoms of ICANS treatment with
corticosteroids and non-sedating-anti-seizure medicinal products
should be instituted as appropriate. Patients should be counselled
on the signs and symptoms of ICANS and that the onset of events may
be delayed. Patients should be instructed to contact their
healthcare professional and seek immediate medical attention should
signs or symptoms occur at any time. Tepkinly should be delayed or
discontinued as recommended.
Serious infections
Treatment with Tepkinly may lead to an increased risk of
infections. Serious or fatal infections were observed in patients
treated with Tepkinly in clinical studies. Administration of
Tepkinly should be avoided in patients with clinically significant
active systemic infections. As appropriate, prophylactic
antimicrobials should be administered prior to and during treatment
with Tepkinly. Patients should be monitored for signs and symptoms
of infection, before and after Tepkinly administration, and treated
appropriately. In the event of febrile neutropenia, patients should
be evaluated for infection and managed with antibiotics, fluids and
other supportive care, according to local guidelines.
Tumour Lysis Syndrome (TLS)
TLS has been reported in patients receiving Tepkinly. Patients at
an increased risk for TLS are recommended to receive hydration and
prophylactic treatment with a uric acid lowering agent. Patients
should be monitored for signs or symptoms of TLS, especially
patients with high tumour burden or rapidly proliferative tumours,
and patients with reduced renal function. Patients should be
monitored for blood chemistries and abnormalities should be managed
promptly.
Tumour flare
Tumour flare has been reported in patients treated with Tepkinly.
Manifestations could include localized pain and swelling.
Consistent with the mechanism of action of Tepkinly, tumour
flare is likely due to the influx of T-cells into tumour sites
following Tepkinly administration. There are no specific risk
factors for tumour flare that have been identified; however,
there is a heightened risk of compromise and morbidity due to mass
effect secondary to tumour flare in patients with bulky tumours
located in close proximity to airways and/or a vital organ.
Patients treated with Tepkinly should be monitored and evaluated
for tumour flare at critical anatomical sites.
CD20-negative disease
There are limited data available on patients with CD20-negative
DLBCL treated with Tepkinly, and it is possible that patients with
CD20-negative DLBCL may have less benefit compared to patients with
CD20-positive DLBCL. The potential risks and benefits associated
with treatment of patients with CD20-negative DLBCL with Tepkinly
should be considered.
Immunisation
Live and/or live-attenuated vaccines should not be given during
Tepkinly therapy. Studies have not been conducted in patients who
received live vaccines.
Fertility, pregnancy and lactation
Tepkinly is not
recommended during pregnancy and in women of childbearing potential
not using contraception.
Effects on ability to drive and use machines
Tepkinly
has minor influence on the ability to drive and use machines. Due
to the potential for ICANS, patients should be advised to exercise
caution while (or avoid if symptomatic) driving, cycling or using
heavy or potentially dangerous machines.
Undesirable effects
Summary of the safety profile
The most common adverse reactions (≥ 20%) were CRS, fatigue,
neutropenia, injection site reactions, musculoskeletal pain,
abdominal pain, pyrexia, nausea, and diarrhoea. Serious adverse
reactions occurred in 52% of patients. The most frequent serious
adverse reaction (≥ 10%) was cytokine release syndrome (31%).
Seven patients (4.2%) experienced a fatal adverse reaction
(pneumonia in 3 (1.8%) patients, viral infection in 3 (1.8%)
patients and ICANS in 1 (0.6%) patient). Adverse reactions that led
to discontinuation occurred in 6.6% of patients. Discontinuation of
Tepkinly due to pneumonia occurred in 6 (3.6%) patients, viral
infection in 3 (1.8%) patients, and CRS, ICANS, or fatigue in 1
(0.6%) patient each. Dose delays due to adverse reactions occurred
in 32% of patients. Adverse reactions leading to dose delays (≥ 3%)
were viral infections (9.6%), CRS (7.2%), neutropenia (4.8%),
pyrexia (3.0%), and thrombocytopenia (3.0%).
This is not a complete summary of all safety
information.
See Tepkinly® full Summary
of Product Characteristics (SmPC) at
www.ema.europa.eu
Globally, prescribing information
varies; refer to the individual country product label for complete
information.
EPKINLY™ (epcoritamab-bysp) U.S. IMPORTANT SAFETY
INFORMATION
Important Warnings—EPKINLY can cause serious side effects,
including:
- Cytokine Release Syndrome (CRS). CRS is common
during treatment with EPKINLY and can be serious or
life-threatening. Tell your healthcare provider or get medical help
right away if you develop symptoms of CRS, including fever of
100.4°F (38°C) or higher, dizziness or lightheadedness, trouble
breathing, chills, fast heartbeat, feeling anxious, headache,
confusion, shaking (tremors), or problems with balance and
movement, such as trouble walking.
Due to the risk of CRS, you will receive EPKINLY on a "step-up"
dosing schedule. The step-up dosing schedule is when you
receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of
your first cycle of treatment (cycle 1). You will receive your
first full dose of EPKINLY on day 15 of cycle 1. If your dose of
EPKINLY is delayed for any reason, you may need to repeat the
step-up dosing schedule. Before each dose in cycle 1, you will
receive medicines to help reduce your risk of CRS. Your healthcare
provider will decide if you need to receive medicine to help reduce
your risk of CRS with future cycles.
- Neurologic problems. EPKINLY can cause serious
neurologic problems that can be life-threatening and lead to death.
Neurologic problems may happen days or weeks after you receive
EPKINLY. Your healthcare provider may refer you to a healthcare
provider who specializes in neurologic problems. Tell your
healthcare provider right away if you develop any symptoms of
neurologic problems, including trouble speaking or writing,
confusion and disorientation, drowsiness, tiredness or lack of
energy, muscle weakness, shaking (tremors), seizures, or memory
loss.
Due to the risk of CRS and neurologic problems, you
should be hospitalized for 24 hours after receiving your first full
dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will
monitor you for symptoms of CRS and neurologic problems during
treatment with EPKINLY, as well as other side effects, and treat
you if needed. Your healthcare provider may temporarily stop or
completely stop your treatment with EPKINLY if you develop CRS,
neurologic problems, or any other side effects that are severe.
Do not drive or use heavy or potentially dangerous
machinery if you develop dizziness, confusion, tremors, drowsiness,
or any other symptoms that impair consciousness until your symptoms
go away. These may be symptoms of CRS or neurologic problems.
EPKINLY can also cause other serious side effects,
including:
- Infections. EPKINLY can cause serious infections
that may lead to death. Your healthcare provider will check you for
symptoms of infection before and during treatment. Tell your
healthcare provider right away if you develop any symptoms of
infection during treatment, including fever of 100.4°F (38°C) or
higher, cough, chest pain, tiredness, shortness of breath, painful
rash, sore throat, pain during urination, or feeling weak or
generally unwell.
- Low blood cell counts. Low blood cell counts are
common during treatment with EPKINLY and can be serious or severe.
Your healthcare provider will check your blood cell counts during
treatment. EPKINLY may cause low blood cell counts,
including low white blood cell counts (neutropenia),
which can increase your risk for infection; low red blood
cell counts (anemia), which can cause tiredness and shortness
of breath; and low platelet counts (thrombocytopenia),
which can cause bruising or bleeding problems.
Your healthcare provider may temporarily stop or completely stop
treatment with EPKINLY if you develop certain side effects.
Before you receive EPKINLY, tell your healthcare provider
about all of your medical conditions, including if you:
- have an infection.
- are pregnant or plan to become pregnant. EPKINLY may harm your
unborn baby. Females who are able to become
pregnant: Your healthcare provider should do a pregnancy
test before you start treatment with EPKINLY. You should use
effective birth control (contraception) during treatment and for 4
months after your last dose of EPKINLY. Tell your healthcare
provider if you become pregnant or think that you may be pregnant
during treatment with EPKINLY.
- are breastfeeding or plan to breastfeed. It is not known if
EPKINLY passes into your breast milk. Do not breastfeed during
treatment with EPKINLY and for 4 months after your last dose of
EPKINLY.
Tell your healthcare provider about all of the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
The most common side effects of EPKINLY include CRS,
tiredness, muscle and bone pain, injection site reactions, fever,
stomach-area (abdominal) pain, nausea, and diarrhea.
These are not all the possible side effects of EPKINLY. Call
your doctor for medical advice about side effects.
You are encouraged to report side effects to the FDA at (800)
FDA-1088 or www.fda.gov/medwatch or to Genmab US,
Inc. at 1-855-4GENMAB (1-855-443-6622).
Please see the Full Prescribing
Information and Medication Guide, including Important
Warnings.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care
for multiple blood cancers while advancing a dynamic pipeline of
investigational therapies across a range of cancer types. Our
dedicated and experienced team joins forces with innovative
partners to accelerate the delivery of potential breakthrough
medicines. We are evaluating more than 20 investigational medicines
in over 300 clinical trials across some of the world's most
widespread and debilitating cancers. As we work to have a
remarkable impact on people's lives, we are committed to exploring
solutions to help patients obtain access to our cancer medicines.
For more information, please
visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines
and solutions that solve serious health issues today and address
the medical challenges of tomorrow. We strive to have a remarkable
impact on people's lives across several key therapeutic areas –
immunology, oncology, neuroscience, and eye care – and products and
services in our Allergan Aesthetics portfolio. For more information
about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on
LinkedIn, Facebook, Instagram, X (formerly Twitter), and
YouTube.
AbbVie Forward-Looking Statements
Some statements in this news release are, or may be
considered, forward-looking statements for purposes of the Private
Securities Litigation Reform Act of 1995. The words "believe,"
"expect," "anticipate," "project" and similar expressions and uses
of future or conditional verbs, generally identify forward-looking
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are subject to risks and uncertainties that may cause actual
results to differ materially from those expressed or implied in the
forward-looking statements. Such risks and uncertainties include,
but are not limited to, challenges to intellectual property,
competition from other products, difficulties inherent in the
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action, and changes to laws and regulations applicable to our
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AbbVie's operations is set forth in Item 1A, "Risk Factors," of
AbbVie's 2022 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no
obligation, and specifically declines, to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by law.
1 Sehn, Salles. "Diffuse Large B-Cell Lymphoma." N
Engl J Med. 2021;384:842-858. DOI: 10.1056/NEJMra2027612.
2 European Medicines Agency. Conditional Marketing
Authorisation. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000925.jsp.
Accessed August 2023.
3 First-in-human (FIH) trial in patients with
relapsed, progressive or refractory B-cell lymphoma -
clinicaltrials.gov. in. (n.d.).
https://classic.clinicaltrials.gov/ct2/show/NCT03625037. Accessed
August 2023.
4 Engelberts et al. "DuoBody-CD3xCD20 induces potent
T-cell-mediated killing of malignant B cells in preclinical models
and provides opportunities for subcutaneous dosing." EBioMedicine.
2020;52:102625. DOI: 10.1016/j.ebiom.2019.102625.
5 Rafiq, Butchar, Cheney, et al. "Comparative Assessment
of Clinically Utilized CD20-Directed Antibodies in Chronic
Lymphocytic Leukemia Cells Reveals Divergent NK Cell, Monocyte, and
Macrophage Properties." J. Immunol. 2013;190(6):2702-2711. DOI:
10.4049/jimmunol.1202588.
6 Singh, Gupta, Almasan. "Development of Novel
Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on
Cell Surface: Looking to Improve Immunotherapy Response." J Cancer
Sci Ther. 2015;7(11):347-358. DOI: 10.4172/1948-5956.1000373.
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