Company Announcement
- Positive CHMP opinion based on results from the Phase 1/2
EPCORE® NHL-1 study
- FL is the second most common type of NHL and accounts for
approximately 20-30 percent of all global cases
- If approved, epcoritamab (TEPKINLY®) would become the first
and only 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 systemic
therapy
Genmab A/S (Nasdaq: GMAB) today announced that the
European Medicines Agency's (EMA) Committee for Medicinal Products
for Human Use (CHMP) has adopted a positive opinion recommending
the granting of conditional marketing authorization of epcoritamab
(TEPKINLY®), a T-cell engaging bispecific antibody administered
subcutaneously, 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. The final European
Commission decision on this indication for epcoritamab is
anticipated later this year.
“Many people living with follicular lymphoma that has either
relapsed or is refractory to existing therapies experience
significant treatment challenges with poor prognosis,” said Jan van
de Winkel, Ph.D., Chief Executive Officer of Genmab. “This positive
opinion recognizes the unmet need in the European Union for
patients whose follicular lymphoma is considered difficult-to-treat
and that epcoritamab may represent a new therapeutic option.”
The CHMP opinion is supported by overall and complete response
data from the Phase 1/2 EPCORE® NHL-1 clinical trial in 128
patients with R/R FL treated with epcoritamab after two or more
lines of systemic therapy. The study included patients who were
refractory to both anti-CD20 monoclonal antibody therapy and an
alkylating agent, patients who were refractory to last prior
treatment, and patients whose disease progressed within two years
of first systemic therapy. In the trial, the most common (≥10%)
adverse reactions were CRS, injection site reactions, pyrexia,
neutropenia, anemia, thrombocytopenia, diarrhea, nausea, headache,
upper respiratory tract infection, pneumonia, and rash.
An additional cohort of 86 patients evaluated an optimized
step-up dosing (SUD) schedule to reduce the incidence and severity
of cytokine release syndrome (CRS), which is an associated side
effect from immune-engaging cancer treatments. Hospitalization was
not mandatory in the optimization cohort. The incidence of CRS was
49% (42 of 86 patients; 9% were grade 2) and there were no grade 3
or higher CRS events in the optimization cohort. The EPCORE NHL-1
results, including results from the optimization cohort, were
recently published in the Lancet Haematology. Additionally, data
from the optimization cohort were presented at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting, selected to be
a part of Best of ASCO® (July 19-20, Boston, MA), and were
presented at the 2024 European Hematology Association (EHA)
Congress.
“Each year, thousands of people in Europe are diagnosed with
follicular lymphoma and it’s an upsetting reality that many of them
will experience relapse and refractory disease,” said Catherine
Thieblemont, M.D., Ph.D., head of the hemato-oncology department,
Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux
de Paris (APHP) in Paris. “Patients deserve new treatment options,
and this positive opinion is the first step to bringing epcoritamab
to more patients who need it.”
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 Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of
non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.i
Although FL is an indolent lymphoma, it is considered incurable
with conventional therapy and patients who achieve remission also
often experience relapse.iii,iv,ii Generally, with each relapse,
the remission and time to next treatment is shorter.iii,iv
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.v
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)
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.
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.
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 Lymphoma Research Foundation official
website.
https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/relapsedfl/.
Accessed February 2024.
iii 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.15708
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/curroncol30050352
v 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20240627569754/en/
Marisol Peron, Senior Vice President, Global Communications
& Corporate Affairs T: +1 609 524 0065; E: mmp@genmab.com
Andrew Carlsen, Vice President, Head of Investor Relations T:
+45 3377 9558; E: acn@genmab.com
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