Company Announcement
- TEPKINLY®
(epcoritamab) is the first and
only subcutaneous bispecific
antibody approved as a monotherapy for adult patients
with relapsed or refractory
(R/R)
diffuse large B-cell lymphoma
(DLBCL) 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, which
demonstrated 62
percent overall
response rate, 39 percent
complete response,
and 15.5-month median
duration of response
in challenging-to-treat R/R DLBCL patients
- Epcoritamab represents the
eighth approved medicine
incorporating
Genmab innovation and fourth created
via Genmab’s DuoBody®
technology platform
COPENHAGEN, Denmark; September
25, 2023 –
Genmab A/S (Nasdaq:
GMAB) announced today 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. 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.i
“With TEPKINLY, people in Europe living with relapsed or
refractory diffuse large B-cell lymphoma who are in need of
additional treatment options now have a readily available,
innovative therapeutic option for this aggressive cancer,” said Jan
van de Winkel, Ph.D., Chief Executive Officer of Genmab. “Today’s
approval underscores our commitment to bringing our bispecific
antibody to more patients worldwide. We’re excited to continue
working with our partner AbbVie to further explore epcoritamab as
potential core therapy across B-cell malignancies.”
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 (n=86) and a complete response rate of 39 percent (n=54),
with a median duration of response of 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 confirmatory comprehensive data will need
to be provided subsequently to maintain the marketing
authorization.ii
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. AbbVie will
continue to pursue regulatory submissions for epcoritamab across
international markets throughout the year.
About the EPCORE™ NHL-1 TrialEPCORE™ NHL-1 is
an open-label, multi-center preliminary efficacy and safety trial
of epcoritamabthat includes a phase 1 first-in-human, dose
escalation part; a phase 2a expansion part; and a dose 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 (NHL), including large B-cell
lymphoma (LBCL) and diffuse large B-cell lymphoma (DLBCL).iii Data
from the dose escalation part of the study, which determined the
recommended phase 2 dose, were published in September 2021.iv In
the phase 2 expansion part, additional patients were treated with
epcoritamab to further explore the efficacy and safety of
epcoritamab in three cohorts of patients with different types of
relapsed or refractory (R/R) B-cell NHLs who had limited
therapeutic options.iii
The median number of prior therapies was three (range: 2 to 11),
with 30 percent receiving two prior therapies, 30 percent receiving
three prior therapies, and 40 percent receiving four or more prior
therapies. Eighteen percent had prior autologous hematopoietic stem
cell transplantation (HSCT), and 39 percent had prior chimeric
antigen receptor (CAR) T-cell therapy. Eighty-two percent of
patients had disease refractory to last therapy and 29 percent of
patients were refractory to CAR T-cell therapy.
The primary endpoint of the phase 2 expansion part was overall
response rate as assessed by an independent review committee.
Secondary efficacy endpoints included duration of response,
complete response rate, progression-free survival, overall
survival, time to response, time to next therapy, and rate of
minimal residual disease negativity. More information can be found
on www.clinicaltrials.gov.
About TEPKINLY (epcoritamab)Epcoritamab is an
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. 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.v 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.vi,vii
Epcoritamab-bysp (EPKINLYTM) was approved under accelerated
approval in the United States in May 2023. Continued approval is
contingent upon verification and description of clinical benefit in
a confirmatory trial(s). For more information, please see the Full
Prescribing Information and Medication Guide, including
Important Warnings.
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. This includes three ongoing
phase 3, open-label, randomized trials including a trial evaluating
epcoritamab as a monotherapy in patients with R/R DLBCL (NCT:
04628494) compared to investigators choice chemotherapy, a phase 3,
trial evaluating epcoritamab in combination with R-CHOP in adult
participants with newly diagnosed DLBCL (NCT: 05578976), and a
phase 3, open-label clinical trial evaluating epcoritamab in
combination in patients with R/R follicular lymphoma (FL) (NCT:
05409066). Epcoritamab is not approved to treat newly diagnosed
patients with DLBCL or FL. The safety and efficacy of epcoritamab
has not been established for these investigational uses. Please
visit clinicaltrials.gov for more information.
EU Indications and Important Safety Information
about Tepkinly®
q (epcoritamab)
IndicationsTepkinly
(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
ContraindicationsHypersensitivity to the active
substance or to any of the excipients.
Special warnings and precautions for
useCytokine 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 infectionsTreatment 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 flareTumour 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.
ImmunisationLive 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 lactationTepkinly is
not recommended during pregnancy and in women of childbearing
potential not using contraception.
Effects on ability to drive and use
machinesTepkinly 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 effectsSummary of the safety
profileThe 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.euGlobally, prescribing
information varies; refer to the individual country product label
for complete information.
About Genmab Genmab is an international
biotechnology company with a core purpose guiding its unstoppable
team to strive towards improving the lives of patients through
innovative and differentiated antibody therapeutics. For more than
20 years, its passionate, innovative and collaborative team has
invented next-generation antibody technology platforms and
leveraged translational research and data sciences, which has
resulted in a proprietary pipeline including bispecific T-cell
engagers, next-generation immune checkpoint modulators, effector
function enhanced antibodies and antibody-drug conjugates. To help
develop and deliver novel antibody therapies to patients, Genmab
has formed 20+ strategic partnerships with biotechnology and
pharmaceutical companies. By 2030, Genmab’s vision is to transform
the lives of people with cancer and other serious diseases with
Knock-Your-Socks-Off (KYSO™) antibody medicines.
Established in 1999, Genmab is headquartered in Copenhagen,
Denmark with locations in Utrecht, the Netherlands, Princeton, New
Jersey, U.S. and Tokyo, Japan. For more information, please visit
Genmab.com and follow us on Twitter.com/Genmab.
Contact: Marisol
Peron, Senior Vice President, Global Communications & Corporate
AffairsT: +1 609 524 0065; E: mmp@genmab.com
Andrew Carlsen, Vice President, Head of Investor RelationsT: +45
3377 9558; E: acn@genmab.comThis Company Announcement contains
forward looking statements. The words “believe”, “expect”,
“anticipate”, “intend” and “plan” and similar expressions identify
forward looking statements. Actual results or performance may
differ materially from any future results or performance expressed
or implied by such statements. The important factors that could
cause our actual results or performance to differ materially
include, among others, risks associated with pre-clinical and
clinical development of products, uncertainties related to the
outcome and conduct of clinical trials including unforeseen safety
issues, uncertainties related to product manufacturing, the lack of
market acceptance of our products, our inability to manage growth,
the competitive environment in relation to our business area and
markets, our inability to attract and retain suitably qualified
personnel, the unenforceability or lack of protection of our
patents and proprietary rights, our relationships with affiliated
entities, changes and developments in technology which may render
our products or technologies obsolete, and other factors. For a
further discussion of these risks, please refer to the risk
management sections in Genmab’s most recent financial reports,
which are available on www.genmab.com and the risk factors included
in Genmab’s most recent Annual Report on Form 20-F and other
filings with the U.S. Securities and Exchange Commission (SEC),
which are available at www.sec.gov. Genmab does not undertake any
obligation to update or revise forward looking statements in this
Company Announcement nor to confirm such statements to reflect
subsequent events or circumstances after the date made or in
relation to actual results, unless required by law. Genmab A/S
and/or its subsidiaries own the following trademarks: Genmab®; the
Y-shaped Genmab logo®; Genmab in combination with the Y-shaped
Genmab logo®; HuMax®; DuoBody®; HexaBody®; DuoHexaBody®,HexElect®
and KYSO™. EPCORE™, EPKINLY™, TEPKINLY® and their
designs are trademarks of AbbVie Biotechnology Ltd.
i Sehn, Salles. "Diffuse Large B-Cell Lymphoma." N Engl J Med.
2021;384:842-858. DOI: 10.1056/NEJMra2027612.ii 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.iii 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
July 5, 2023.iv Hutchings M, Mous R, Roost Clausen M, et al. Dose
escalation of subcutaneous epcoritamab in patients with relapsed or
refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2
study. The Lancet. Published Online September 8, 2021;volume 398,
Issue 10306, P-1157-1169.v 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.vi 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.vii 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.
Company Announcement no. 41 CVR no. 2102 3884 LEI Code
529900MTJPDPE4MHJ122
Genmab A/SCarl Jacobsens Vej 302500 Valby Denmark
- 230925_CA_TEPKINLY EMA Approval
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