Company Announcement
- TEPKINLY is the first and only
subcutaneous bispecific antibody 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 systemic therapy
COPENHAGEN, Denmark; August 19, 2024 –
Genmab A/S (Nasdaq: GMAB) 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 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 the
European Economic Area (EEA) countries (Iceland, Liechtenstein,
Norway) and Northern Ireland.
“Follicular lymphoma can be challenging to treat and today’s
approval of TEPKINLY for the treatment of relapsed/refractory
follicular lymphoma after two or more lines of systemic therapy
marks an important milestone for patients in the European Union who
are in need of more options offering a balance of meaningful
efficacy and favorable safety,” said Jan van de Winkel, Ph.D.,
President and Chief Executive Officer of Genmab. “Alongside our
partner AbbVie, we are committed to exploring the continued
development of epcoritamab as a potential core therapy across
B-cell malignancies.”
FL is typically a slow-growing form of Hodgkin’s lymphoma (NHL)
that arises from B-cell lymphocytes. FL is the second most common
form of NHL overall, accounting for 20-30 percent of all NHL cases,
and represents 10-20 percent of all lymphomas in the western
world.i FL is considered incurable, and there is no standard of
care treatment for third-line or later FL.i,ii Patients who achieve
remission also often experience relapse.iii,iv,v
The conditional marketing authorization is supported by data
from the 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. Patients included in the study 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 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 diffuse large B-cell lymphoma (DLBCL) cohort. 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 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.
“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 can be 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.”
About the 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 or refractory 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 expansion part generated pivotal data from patients with FL and
DLBCL. The optimization part evaluated additional CRS mitigation
strategies during cycle 1. The primary endpoint of the expansion
part was overall response rate (ORR) as assessed by an Independent
Review Committee (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.
About EpcoritamabEpcoritamab 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.vi
Epcoritamab (approved under the brand name EPKINLY in the U.S.
and Japan, and TEPKINLY in the EU) has received regulatory approval
in certain lymphoma indications in several territories. Epcoritamab
is being co-developed by Genmab and AbbVie 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
investigational R/R FL indication and additional approvals for the
R/R DLBCL indication.
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 four ongoing Phase
3, open-label, randomized trials including a trial evaluating
epcoritamab as a monotherapy in patients with R/R DLBCL compared to
investigators choice chemotherapy (NCT04628494), a trial evaluating
epcoritamab in combination with R-CHOP in adult participants with
newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab
in combination with rituximab and lenalidomide (R2) in patients
with R/R FL (NCT05409066), and a trial evaluating epcoritamab in
combination with rituximab and lenalidomide (R2) compared to
chemoimmunotherapy in patients with previously untreated FL
(NCT06191744). The safety and efficacy of epcoritamab has not been
established for these investigational uses. Please
visit www.clinicaltrials.gov for more information.
EU Indications and Important Safety Information about
Tepkinly®
(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.
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
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. 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 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 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.
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 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 Genmab Genmab is an international
biotechnology company with a core purpose of guiding its
unstoppable team to strive toward improving the lives of patients
with innovative and differentiated antibody therapeutics. For 25
years, its passionate, innovative and collaborative team has
invented next-generation antibody technology platforms and
leveraged translational, quantitative and data sciences, resulting
in a proprietary pipeline including bispecific T-cell engagers,
antibody-drug conjugates, next-generation immune checkpoint
modulators and effector function-enhanced antibodies. 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 international presence across North America, Europe
and Asia Pacific. For more information, please
visit Genmab.com and follow us
on LinkedIn and X.
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.com
This Media Release 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 Media Release 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 Lymphoma Research Foundation official website.
https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed February
2024.ii Ghione P, Palomba ML, Ghesquieres H, et al. Treatment
patterns and outcomes in relapsed/refractory follicular lymphoma:
results from the international SCHOLAR-5 study. Haematologica.
2023;108(3):822-832. doi: 10.3324/haematol.2022.281421.iii Lymphoma
Research Foundation official website.
https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/relapsedfl/.
Accessed February 2024.iv Kuruvilla J, Ewara EM, Elia-Pacitti J, et
al. Estimating the Burden of Illness of Relapsed Follicular
Lymphoma and Marginal Zone Lymphoma in Ontario, Canada. Curr
Oncol. 2023;30(5):4663-4676. doi:10.3390/curroncol30050352v
Rivas‐Delgado, A., Magnano, L., Moreno‐Velázquez, et al. Response
duration and survival shorten after each relapse in patients with
follicular lymphoma treated in the rituximab era. Br J Haematol.
2018;184(5):753-759. doi:10.1111/bjh.15708vi 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
dosing. EBioMedicine. 2020;52:102625. doi:
10.1016/j.ebiom.2019.102625.
Company Announcement no. 55 CVR no. 2102 3884 LEI Code
529900MTJPDPE4MHJ122
Genmab A/SCarl Jacobsens Vej 302500 Valby Denmark
- 190824_CA55_TEPKINLY FL EU Approval
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