- A supplementary Biologics License Application
(sBLA) is supported by data from the Phase 1/2 EPCORE™ NHL-1
clinical trial in patients with relapsed or refractory (R/R)
follicular lymphoma (FL), demonstrating strong and durable
treatment responses
- In November 2023,
the FDA granted this investigational indication a Breakthrough
Therapy Designation (BTD)
NORTH
CHICAGO, Ill., Feb. 27,
2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that the U.S. Food and Drug Administration (FDA) has
granted Priority Review of the supplemental Biologics License
Application (sBLA) for epcoritamab-bysp, a subcutaneously
administered T-cell engaging bispecific antibody for the treatment
of adult relapsed or refractory (R/R) follicular lymphoma (FL)
after two or more lines of therapy. If approved, epcoritamab-bysp
(EPKINLY®) will be the first and only subcutaneous
bispecific antibody to treat adults with R/R FL after two lines of
prior therapy, marking its second indication following FDA and
European Medicines Agency (EMA) approval of R/R third-line diffuse
large B-cell lymphoma (DLBCL) treatment.
The FDA grants Priority Review to investigational therapies
that, if approved, may offer significant improvements in the safety
or effectiveness of the treatment, diagnosis or prevention of
serious conditions when compared to standard applications. This
designation shortens the review period to six months compared to 10
months for Standard Review. In addition, the investigational R/R FL
indication was granted Breakthrough Therapy Designation by the FDA
and was submitted to the EMA in November
2023.
"Despite new treatment options, follicular lymphoma remains
incurable and difficult to treat. Unfortunately, relapse is common
and additional lines of treatment are needed," said Mariana Cota Stirner, M.D., Ph.D., vice
president, therapeutic area head for hematology, AbbVie. "Together
with our partner Genmab, we are committed to further advancing
epcoritamab as a core lymphoma therapy."
The sBLA is based on results from the Phase 1/2 EPCORE™ NHL-1
clinical trial, which demonstrated high overall and complete
responses in patients with R/R FL after two or more lines of
therapy treated with epcoritamab. Data from the FL cohorts of the
trial were presented at the Annual Meeting and Exposition of
the American Society of Hematology (ASH) in December 2023. The optimization cohort evaluated
an alternative step-up dosing to reduce the risk and severity of
cytokine release syndrome (CRS) and to support
potential outpatient administration.
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 investigational R/R FL
indication and additional approvals for the R/R DLBCL
indication.
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 after two or more
lines of systemic therapy. 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 further minimize Grade 2 cytokine
release syndrome (CRS) and mitigate Grade ≥3 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.
About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of non-Hodgkin's
lymphoma (NHL) that arises from B-lymphocytes.1 FL is
the second most common form of NHL, accounting for 20-30% of all
NHL cases, and represents 10-20% of all lymphomas in the western
world.2,3 Although FL is an indolent lymphoma, it
is considered incurable with conventional therapy and patients who
achieve remission often experience relapse.4,5,6
Additionally, with each relapse the remission and time to next
treatment is shorter7, adding increased cost to the
health system and negatively impacting the patient's quality of
life.8
About Epcoritamab
Epcoritamab is an investigational
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.9
Epcoritamab (approved under the brand name
EPKINLY® in the United States and
TEPKINLY® in the European Union) has received
regulatory approval in adults with certain types of large B-cell
lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL),
globally. 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. Use of epcoritamab in FL is not approved in the U.S. or in
the EU. AbbVie will continue to pursue regulatory submissions for
epcoritamab across international markets.
Genmab and AbbVie continue to evaluate the use of epcoritamab as
a monotherapy, and in combination, across different 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 investigator's choice
chemotherapy, a Phase 3 trial evaluating epcoritamab in combination
with R-CHOP in adult patients with newly diagnosed DLBCL (NCT:
05578976), and a Phase 3 clinical trial evaluating epcoritamab in
combination with rituximab and lenalidomide (R2) in
patients with R/R FL (NCT: 05409066). Epcoritamab is not approved
to treat patients with newly diagnosed DLBCL or with FL. The safety
and efficacy of epcoritamab has not been established for these
investigational uses. Please visit clinicaltrials.gov for more
information.
EPKINLY™ (epcoritamab-bysp) U.S. USE and IMPORTANT
SAFETY INFORMATION USE
EPKINLY is a prescription
medicine used to treat adults with certain types of diffuse large
B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma that has
come back (relapsed) or that did not respond to previous treatment
(refractory), and who have received 2 or more treatments for their
cancer.
EPKINLY is approved based on patient response data. A study is
ongoing to confirm the clinical benefit of EPKINLY. It is not known
if EPKINLY is safe and effective in children.
IMPORTANT SAFETY INFORMATION FOR EPKINLY IN R/R
DLBCL
Important Warnings—EPKINLY can cause serious side
effects, including:
- Cytokine release syndrome (CRS), which is common during
treatment with EPKINLY and can be serious or life-threatening. To
help reduce your risk of CRS, you may receive other medicines
before receiving EPKINLY and you will also be given smaller doses
of EPKINLY for the first 2 doses (called "step-up" dosing). Your
first full dose of EPKINLY will be given on day 15 of your first
cycle of treatment and you should be hospitalized for 24 hours
after due to risk of CRS and neurologic problems. If your dose of
EPKINLY is delayed for any reason, you may need to repeat the
step-up dosing schedule.
- Neurologic problems that can be life-threatening and
lead to death. Neurologic problems may happen days or weeks after
you receive EPKINLY.
Tell your healthcare provider or get medical help right
away if you develop a fever of 100.4°F (38°C) or higher;
dizziness or lightheadedness; trouble breathing; chills; fast
heartbeat; feeling anxious; headache; confusion; shaking (tremors);
problems with balance and movement, such as trouble walking;
trouble speaking or writing; confusion and disorientation;
drowsiness, tiredness or lack of energy; muscle weakness; seizures;
or memory loss. These may be symptoms of CRS or neurologic
problems. Do not drive or use heavy machinery or do other
dangerous activities if you have any symptoms that impair
consciousness until your symptoms go away.
EPKINLY can cause other serious side effects,
including:
- Infections that may lead to death. 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 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 cells
(neutropenia), which can increase your risk for infection; low red
blood cells (anemia), which can cause tiredness and shortness of
breath; and low platelets (thrombocytopenia), which can cause
bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS,
neurologic problems, infections, and low blood cell counts during
treatment with EPKINLY. 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 your medical conditions, including if you have an
infection, are pregnant or plan to become pregnant, or are
breastfeeding or plan to breastfeed. If you receive EPKINLY while
pregnant, it may harm your unborn baby. If you are a female who
can become pregnant, your healthcare provider should do a
pregnancy test before you start treatment with EPKINLY and 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. Do not breastfeed
during treatment with EPKINLY and for 4 months after your last dose
of EPKINLY.
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 Medication Guide, including
Important Warnings.
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 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
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 2023 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 Lymphoma Research Foundation
official website. https://lymphoma.org/aboutlymphoma/nhl/fl/.
Accessed February 2024.
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2 Ma S.
Risk factors of follicular lymphoma. Expert Opin Med
Diagn. 2012;6:3232333. doi:
10.1517/17530059.2012.686996.
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3 Luminari S, Bellei M, Biasoli I,
Federico M. Follicular lymphoma—treatment and prognostic
factors. Rev Bras Hematol Hemoter. 2012;34:54-59.
doi: 10.5581/1516-8484.20120015.
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4 Link
BK, Day BM, Zhou Z, et al. Second-Line and Subsequent Therapy and
Outcomes for Follicular Lymphoma in the United States: Data From
the Observational National LymphoCare Study. Br J
Haematol. 2019;184(4):660-663. doi:
10.1111/bjh.15149.
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5 Ren
J, Asche CV, Shou Y, Galaznik A. Economic Burden and Treatment
Patterns for Patients With Diffuse Large B-Cell Lymphoma and
Follicular Lymphoma in the USA. J Comp Eff
Res. 2019;8(6):393-402. doi:
10.2217/cer-2018-0094.
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6 Lymphoma Research Foundation
official
website. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/relapsedfl/.
Accessed February 2024.
|
7 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
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8 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
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9 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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