- EPKINLY is now the first and only bispecific antibody
approved in the U.S. to treat both relapsed or refractory (R/R)
follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma
(DLBCL)
- Bispecific antibodies are designed to induce targeted cell
killing by engaging the immune system
- FL is considered incurable with current standard of care
therapies. Many people living with FL who have relapsed or
are refractory to existing therapies have limited treatment
options and reduced survival1
NORTH
CHICAGO, Ill., June 26,
2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that the U.S. Food and Drug Administration (FDA) has
approved EPKINLY® (epcoritamab-bysp) as the first and
only T-cell engaging bispecific antibody administered
subcutaneously for the treatment of adults with relapsed or
refractory (R/R) follicular lymphoma (FL) after two or more lines
of prior therapy. This indication is approved under the FDA's
Accelerated Approval program based on overall response rate (ORR)
and durability of response. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in a confirmatory trial(s).
"The FDA approval of EPKINLY offers a new treatment option for
relapsed or refractory follicular lymphoma, particularly following
failure of other therapies," said Mariana
Cota Stirner, M.D., Ph.D., vice president, therapeutic area
head for hematology, AbbVie. "EPKINLY treatment has shown deep and
durable responses for many patients. Subcutaneous dosing offers
convenience, and EPKINLY can be given to patients without mandatory
hospitalization using a 3-step-up dosing regimen. We believe that
EPKINLY has the potential to be a core therapy in the treatment of
multiple B-cell malignancies and furthers our company mission to
advance research to raise standards of care for patients with
cancer."
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.
FL is typically an indolent (or 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 About 15,000 people develop FL each year in
the U.S.3 and it is considered incurable with current
standard of care therapies.4 Patients often relapse and,
with each relapse the remission and time to next treatment is
shorter.5 Over time, transformation to DLBCL, an
aggressive form of NHL associated with poor survival outcomes, can
occur in more than 25% of FL patients.6
"Patients with relapsed or refractory follicular lymphoma face
significant treatment challenges, and there is currently no clear
standard of care treatment available across practice settings,"
said Jeff Sharman, M.D., Disease
Chair, Hematology Research, Sarah Cannon Research Institute
(SCRI) at Willamette Valley Cancer Institute in Eugene, Oregon. "The responses observed in the
follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, as
well as in patients with relapsed or refractory DLBCL from the
trial, show the potential of EPKINLY to serve as an important
treatment option for these patients."
"People living with follicular lymphoma are in need of
additional options when their cancer returns," said Lee Greenberger, Ph.D., Chief Scientific Officer
at The Leukemia & Lymphoma Society. "Today's approval is
welcome news for patients, as it provides another tool in the
physician arsenal for this difficult-to-treat form of cancer."
FDA approval is based on results from the Phase 1/2
EPCORE® NHL-1 clinical trial, which evaluated the safety
and efficacy of EPKINLY in 127 adult patients with R/R FL who
previously received a median of three lines of therapy and with 70%
having double refractory disease. Results and safety findings
include:
- The study results showed an ORR – the study's primary endpoint
− of 82%, a complete response (CR) rate of 60% and a partial
response (PR) rate of 22%.
- At a median follow-up of 14.8 months among responders,
more than half of patients who responded to treatment in the study
remained responsive to treatment (i.e., median duration of response
was not reached).
- Safety was evaluated in a total of 213 patients:
- The safety of EPKINLY at a target dose of 48 mg was
evaluated in EPCORE NHL-1, a single-arm study of 127 patients who
received a 2-step up dosage schedule.
- The most common (≥20%) adverse reactions were injection site
reactions, cytokine release syndrome (CRS), COVID-19, fatigue,
upper respiratory tract infection, musculoskeletal pain, rash,
diarrhea, fever, cough, and headache.
- A separate dose optimization cohort evaluated 86 patients at
the recommended 3-step dosage schedule for CRS mitigation. For the
first full dose of this 3-step regimen, mandatory hospitalization
was not required. There were no grade 3 CRS observed in patients
with FL who received EPKINLY with the 3 step-up dosage
schedule.
The prescribing information has a Boxed Warning for serious or
life-threatening CRS and immune effector cell-associated
neurotoxicity syndrome (ICANS). Warnings and precautions include
infections, cytopenias, and embryo-fetal toxicity. Please see
additional Important Safety Information, below.
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.
This cohort generated pivotal data from patients with FL and DLBCL.
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.
NCCN® Clinical Practice Guidelines
The
National Comprehensive Cancer Network®
(NCCN®) Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for "B-Cell Lymphomas" were recently
updated (Version 2.2024) to add EPKINLY as a Category 2A, preferred
recommendation for third-line and subsequent therapy for patients
with FL.
About EPKINLY® (epcoritamab-bysp)
EPKINLY
is a prescription medicine used to treat adults with certain types
of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell
lymphoma, or follicular lymphoma (FL) that has come back or that
did not respond to previous treatment after receiving 2 or more
treatments. EPKINLY is approved based on patient response data.
Studies are ongoing to confirm the clinical benefit of EPKINLY. It
is not known if EPKINLY is safe and effective in children.
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.7
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.
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.
EPKINLY® (epcoritamab-bysp) U.S. IMPORTANT SAFETY
INFORMATION
IMPORTANT SAFETY INFORMATION
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 will receive EPKINLY on a step-up
dosing schedule (when you receive 2 or 3 smaller step-up doses of
EPKINLY before your first full dose during your first cycle of
treatment), and you may also receive other medicines before and for
3 days after receiving EPKINLY. 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.
People with DLBCL or high-grade B-cell lymphoma should be
hospitalized for 24 hours after receiving their first full
dose of EPKINLY on day 15 of cycle 1 due to the risk of
CRS and neurologic problems.
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. If you have any symptoms that impair consciousness,
do not drive or use heavy machinery or do other dangerous
activities until your symptoms go away.
EPKINLY can cause other serious side effects,
including:
- Infections that may lead to death. Your healthcare
provider will check you for signs and symptoms of infection before
and during treatment and treat you as needed if you develop an
infection. You should receive medicines from your healthcare
provider before you start treatment to help prevent infection. 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, which 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.
In DLBCL or high-grade B-cell lymphoma, 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. The most common severe abnormal
laboratory test results include decreased white blood cells,
decreased red blood cells, and decreased platelets.
In follicular lymphoma the most common side effects of
EPKINLY include injection site reactions, CRS, COVID-19,
tiredness, upper respiratory tract infections, muscle and bone
pain, rash, diarrhea, fever, cough, and headache. The most
common severe abnormal laboratory test results include
decreased white blood cells and decreased red blood cells.
These are not all of 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 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 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 Salles G, Schuster S, Fischer L; et al. A
Retrospective Cohort Study of Treatment Outcomes of Adult Patients
With Relapsed or Refractory Follicular Lymphoma (ReCORD-FL).
HemaSphere 6(7):p e745, July 2022. |
DOI: 10.1097/HS9.0000000000000745.
2 Lymphoma Research Foundation official website.
https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed February 2024.
3 Leukemia & Lymphoma Society.
https://www.lls.org/research/follicular-lymphoma-fl. Accessed
March 2024.
4 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.
5 Rivas-Delgado A, Magnano L, Moreno-Velázquez M, 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.
6 Al-Tourah AJ, Gill KK, Chhanabhai M, et al.
Population-based analysis of incidence and outcome of transformed
non-Hodgkin's lymphoma. J Clin Oncol. 2008 Nov
10;26(32):5165-9. doi: 10.1200/JCO.2008.16.0283. Epub 2008
Oct 6. PMID: 18838711.
7 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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