- TEPKINLY (epcoritamab) is the first and only
subcutaneous bispecific antibody conditionally approved as a
monotherapy in the European Union to treat both relapsed or
refractory (R/R) follicular lymphoma (FL) and R/R diffuse large
B-cell lymphoma (DLBCL), after two or more lines of prior
therapy
- FL is an incurable form of non-Hodgkin's lymphoma (NHL),
with about 13,000 estimated cases in Western Europe alone each
year1
NORTH
CHICAGO, Ill., Aug. 19,
2024 /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) follicular lymphoma (FL) after two or more lines
of prior therapy. TEPKINLY is the first and only subcutaneous
T-cell engaging bispecific antibody approved to treat both R/R FL
and R/R diffuse large B-cell lymphoma (DLBCL) in the European Union
(EU), as well as the European Economic Area (EEA) countries
(Iceland, Liechtenstein, Norway) and Northern
Ireland.
"The European approval of TEPKINLY for the treatment of
follicular lymphoma after two or more prior treatments is yet
another step forward in our aspiration to develop TEPKINLY as a
potential core therapy across multiple B-cell malignancies. First
approved for the treatment of adult patients with relapsed or
refractory diffuse large B-cell lymphoma, its expansion into
follicular lymphoma underscores its utility as a hematological
cancer treatment," said Mariana Cota
Stirner, M.D., Ph.D., vice president, therapeutic area head
for hematology, AbbVie. "Together with our partner, Genmab, we are
thrilled with today's approval which advances our commitment to
elevating care for people living with cancer."
FL is typically a slow-growing form of non-Hodgkin's lymphoma
(NHL) that arises from B-lymphocytes and is the second most
common form of NHL accounting for 20-30% of all cases.2
FL is considered incurable, and there is no standard of care
treatment for third-line or later FL.2,3 Patients often
relapse and with each relapse, the remission and time to next
treatment is shorter.4 Over time, transformation to
DLBCL, an aggressive form of NHL associated with poor survival
outcomes, can occur in more than 25% of FL
patients.5
"The approval of epcoritamab by the European Commission is a
promising update for the lymphoma community," said Kate Rogers, CEO of the Follicular Lymphoma
Foundation. "Given that relapsed or refractory follicular lymphoma
is a very challenging form of cancer to treat, especially in later
lines of therapy, it is critical that patients and physicians have
additional options when it comes to treating this type of
cancer."
The conditional marketing authorization is supported by data
from Phase 1/2 EPCORE® NHL-1 clinical trial: an
open-label, multi-cohort, multicenter, single-arm trial that
evaluated TEPKINLY as monotherapy in patients with R/R FL after two
or more lines of prior systemic therapy. The study included
patients who were refractory to both anti-CD20 monoclonal antibody
therapy and an alkylating agent (70% having double refractory
disease), patients who were refractory to last prior treatment
(82%), and patients whose disease progressed within two years of
initiating any first systemic therapy (52%). The results published
in the Lancet Haematology showed that patients treated
with TEPKINLY (n=128) had an overall response rate (ORR) of
83% and a complete response (CR) rate of 63%. At a median follow-up
of 16.2 months, the median duration of response was 21.4 months
(13.7, NR). Duration of complete response (DOCR) was not
reached.
The study included a planned separate optimization cohort, which
evaluated 86 patients with the recommended 3-step-up doses for
cytokine release syndrome (CRS) mitigation. Hospitalization was not
mandatory in the cycle 1 optimization cohort. With the optimized
regimen, 40% of patients experienced Grade 1 CRS and 9% experienced
Grade 2 (no Grade 3 or higher CRS were reported). No immune
effector cell-associated neurotoxicity syndrome (ICANS) cases were
reported in this cohort.
The safety profile of epcoritamab in the pivotal cohort was
similar to reports of epcoritamab monotherapy in the pivotal EPCORE
NHL-1 DLBCL cohort.6 In the pooled safety population
(n=382), the most common adverse reactions (≥ 20%) with TEPKINLY
were CRS, injection site reactions, fatigue, viral infection,
neutropenia, musculoskeletal pain, pyrexia, and diarrhea. The most
frequent serious adverse reaction (≥ 10%) was CRS (34%). Fourteen
patients (3.7%) experienced a fatal adverse reaction [pneumonia in
9 (2.4%) patients, viral infection in 4 (1.0%) patients, and ICANS
in 1 (0.3%) patient].
About the Phase 1/2 EPCORE® NHL-1
Trial
EPCORE® NHL-1 is an open-label,
multi-center safety and preliminary efficacy trial of epcoritamab
that consists of three parts: a dose escalation part; an expansion
part; and an optimization part. The trial was designed to evaluate
subcutaneous epcoritamab in patients with relapsed, progressive or
refractory CD20+ mature B-cell non-Hodgkin's lymphoma (B-NHL),
including FL. In the expansion part, additional patients were
enrolled to further explore the safety and efficacy of epcoritamab
in three cohorts of patients with different types of
relapsed/refractory B-NHLs who have limited therapeutic options.
The optimization part evaluates the potential for alternative
step-up dosing regimens to help minimize overall rates and severity
of cytokine release syndrome (CRS). The primary endpoint of the
expansion part was ORR as assessed by an IRC. Secondary efficacy
endpoints included duration of response, complete response rate,
duration of complete response, progression-free survival, and time
to response as determined by the Lugano criteria. Overall survival,
time to next therapy, and rate of minimal residual disease
negativity were also evaluated as secondary efficacy endpoints. The
primary endpoint of the optimization part was the rate of ≥ Grade 2
CRS events and all grade CRS events from first dose of epcoritamab
through 7 days following administration of the second full dose of
epcoritamab.
More information can be found on www.clinicaltrials.gov
(NCT03625037).
About Epcoritamab
Epcoritamab is an IgG1-bispecific
antibody created using Genmab's proprietary
DuoBody® technology and administered
subcutaneously. Genmab's DuoBody-CD3 technology is designed to
direct cytotoxic T cells selectively to elicit an immune response
toward target cell types. Epcoritamab is designed to simultaneously
bind to CD3 on T cells and CD20 on B cells and induces
T-cell-mediated killing of CD20+ cells.
Epcoritamab (approved under the brand name
EPKINLY® in the United States and
TEPKINLY® in the European Union) has received
regulatory approval in certain lymphoma indications in several
countries.
Epcoritamab 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. Both companies
will pursue additional international regulatory approvals for the
R/R FL indication and the R/R DLBCL indication.
AbbVie will continue to pursue regulatory submissions for
epcoritamab across international markets. Both Genmab and AbbVie
continue to evaluate the use of epcoritamab as a monotherapy and in
combination across lines of therapy in a range of hematologic
malignancies. Please visit clinicaltrials.gov for more
information.
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.
Tepkinly as monotherapy is indicated for the treatment of adult
patients with relapsed or refractory follicular lymphoma (FL) 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. 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. Patients
with DLBCL 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.
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. 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. Patients with DLBCL 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.
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 and patients with CD20-negative FL treated with Tepkinly, and
it is possible that patients with CD20-negative DLBCL and
CD20-negative FL may have less benefit compared to patients with
CD20-positive DLBCL and patients with CD20-postitive FL,
respectively. The potential risks and benefits associated with
treatment of patients with CD20-negative DLBCL and FL 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 safety of Tepkinly was evaluated in 382 patients with relapsed
or refractory large B-cell lymphoma (N=167), FL (N=129) and FL
(3-step step-up dose schedule N=86) after two or more lines of
systemic therapy and included all the patients who enrolled to the
48 mg dose and received at least one dose of TEPKINLY. The most
common adverse reactions (≥ 20%) were CRS, injection site
reactions, fatigue, viral infection, neutropenia, musculoskeletal
pain, pyrexia, and diarrhoea.
Serious adverse reactions occurred in 50% of patients. The most
frequent serious adverse reaction (≥ 10%) was cytokine release
syndrome (34%). Fourteen patients (3.7%) experienced a fatal
adverse reaction (pneumonia in 9 (2.4%) patients, viral infection
in 4 (1.0%) patients, and ICANS in 1 (0.3%) patient). Adverse
reactions that led to discontinuation occurred in 6.8% of patients.
Discontinuation of Tepkinly due to pneumonia occurred in 14 (3.7%)
patients, viral infection in 8 (2.1%) patients, fatigue in 2 (0.5%)
patients, and CRS, ICANS, or diarrhoea, in 1 (0.3%) patient
each.
Dose delays due to adverse reactions occurred in 42% of
patients. Adverse reactions leading to dose delays (≥ 3%) were
viral infections (17%), CRS (11%), neutropenia (5.2%), pneumonia
(4.7%), upper respiratory tract infection (4.2%), and pyrexia
(3.7%).
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.
About AbbVie in Oncology
At AbbVie, we are committed
to transforming standards of care for patients living with
difficult-to-treat cancers. We are advancing a dynamic pipeline of
investigational therapies across a range of cancer types in both
blood cancers and solid tumors. We are focusing on creating
targeted medicines that either impede the reproduction of cancer
cells or enable their elimination. We achieve this through various,
targeted treatment modalities including Antibody Drug Conjugates
(ADCs), Immuno-Oncology, and bi-specific and CAR-T platforms. Our
dedicated and experienced team joins forces with innovative
partners to accelerate the delivery of potential breakthrough
medicines.
Today, our expansive oncology portfolio is comprised of approved
and investigational treatments for a wide range of blood and solid
tumors. We are evaluating more than 20 investigational medicines
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
us at 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
statements. AbbVie cautions that these forward-looking statements
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
research and development process, adverse litigation or government
action, and changes to laws and regulations applicable to our
industry. Additional information about the economic, competitive,
governmental, technological and other factors that may affect
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 Kanas G,
Ge W, Quek RGW, et al. Leukemia & Lymphoma.
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in relapsed/refractory follicular lymphoma: results from the
international SCHOLAR-5 study. Haematologica.
2023;108(3):822-832. doi: 10.3324/haematol.2022.281421.
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Rivas-Delgado A, Magnano L, Moreno-Velázquez M, et al. Response
duration and survival shorten after each relapse in patients with
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doi:10.1111/bjh.15708.
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5 Engelberts
PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent
T-cell-mediated killing of malignant B cells in preclinical models
and provides opportunities for subcutaneous
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6 Linton
Kim, Vitolo Umberto, Jurczak Wojciech, et al. Epcoritamab
monotherapy in patients with relapsed or refractory follicular
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