- Updates are supported by data from the Phase 1/2
EPCORE™ NHL-1 clinical trial
CHICAGO, Ill., Nov. 27,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced updates from the U.S. Food and Drug Administration (FDA)
and European Medicines Agency (EMA) for epcoritamab, an
investigational T-cell engaging bispecific antibody administered
subcutaneously, for relapsed or refractory (R/R) follicular
The FDA has granted Breakthrough Therapy Designation (BTD) to
epcoritamab-bysp (EPKINLY®) for the treatment of adult
patients with R/R FL after two or more therapies.
Additionally, the EMA has validated a Type II application for
epcoritamab (TEPKINLY®) for the same indication. If
approved, R/R FL would become the second conditionally approved
indication for epcoritamab in the European Union.
"The FDA granted BTD and validated European application
are an important step in our commitment to improving the lives
of patients with relapsed/refractory follicular lymphoma, a complex
blood cancer with limited treatment options," said Mariana Cota Stirner, M.D., Ph.D., vice
president, therapeutic area head for hematology, AbbVie. "Together
with Genmab, we are continuing to investigate epcoritamab as a
potential core therapy for multiple B-cell malignancies, including
diffuse large B-cell lymphoma and now follicular lymphoma."
These updates were supported by
previously announced results from the Phase 1/2 EPCORE™
NHL-1 clinical trial evaluating the safety and preliminary efficacy
of subcutaneous epcoritamab in 128 adult patients with relapsed,
progressive or refractory CD20+ mature B-cell non-Hodgkin's
lymphoma (NHL), including FL. Data from the FL cohort of
the trial, including an optimized dosing schedule allowing for
outpatient administration, will be presented at the upcoming
Annual Meeting and Exposition of the American Society of Hematology
(ASH) in December 2023.
BTD may expedite the development and review of investigational
medicines by the FDA for serious or life-threatening diseases in
cases where preliminary clinical evidence shows that a therapy may
provide substantial improvements over available
therapies.1 EMA validation confirms that the submitted
regulatory application is complete and initiates the scientific
review process by the EMA's Committee for Medicinal Products for
Human Use (CHMP).
FL is typically an indolent, or slow-growing, form of NHL that
arises from B-cell lymphocytes.2 It is the second most
common form of NHL overall, accounting for 20 percent to 30 percent
of all NHL cases globally.3 Although FL is an indolent
lymphoma, it is considered incurable with current standard of care
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
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 Phase
1 first-in-human, dose escalation part; a Phase 2a expansion part;
and a Phase 2a dose optimization part. The trial was designed to
evaluate subcutaneous epcoritamab in adult patients with relapsed,
progressive or refractory CD20+ mature B-cell non-Hodgkin's
lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a
expansion part, additional patients are being enrolled to further
explore the safety and efficacy of epcoritamab in three cohorts of
patients with different types of relapsed or refractory (R/R)
B-cell NHLs who have limited therapeutic options. The dose
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 application for BTD
included additional data from this cohort of patients. The primary
endpoint of the expansion part was overall response rate as
assessed by an independent review committee. 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.
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.6
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 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. USES AND
IMPORTANT SAFETY INFORMATION
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
Important Warnings—EPKINLY can cause serious side effects,
- Cytokine Release Syndrome (CRS). CRS is common
during treatment with EPKINLY and can be serious or
life-threatening. Tell your healthcare provider or get medical help
right away if you develop symptoms of CRS, including fever of
100.4°F (38°C) or higher, dizziness or lightheadedness, trouble
breathing, chills, fast heartbeat, feeling anxious, headache,
confusion, shaking (tremors), or problems with balance and
movement, such as trouble walking.
Due to the risk of CRS, you will receive EPKINLY on a "step-up"
dosing schedule. The step-up dosing schedule is when you
receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of
your first cycle of treatment (cycle 1). You will receive your
first full dose of EPKINLY on day 15 of cycle 1. If your dose of
EPKINLY is delayed for any reason, you may need to repeat the
step-up dosing schedule. Before each dose in cycle 1, you will
receive medicines to help reduce your risk of CRS. Your healthcare
provider will decide if you need to receive medicine to help reduce
your risk of CRS with future cycles.
- Neurologic problems. EPKINLY can cause serious
neurologic problems that can be life-threatening and lead to death.
Neurologic problems may happen days or weeks after you receive
EPKINLY. Your healthcare provider may refer you to a healthcare
provider who specializes in neurologic problems. Tell your
healthcare provider right away if you develop any symptoms of
neurologic problems, including trouble speaking or writing,
confusion and disorientation, drowsiness, tiredness or lack of
energy, muscle weakness, shaking (tremors), seizures, or memory
Due to the risk of CRS and neurologic problems, you
should be hospitalized for 24 hours after receiving your first full
dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will
monitor you for symptoms of CRS and neurologic problems during
treatment with EPKINLY, as well as other side effects, and treat
you if needed. Your healthcare provider may temporarily stop or
completely stop your treatment with EPKINLY if you develop CRS,
neurologic problems, or any other side effects that are severe.
Do not drive or use heavy or potentially dangerous
machinery if you develop dizziness, confusion, tremors, drowsiness,
or any other symptoms that impair consciousness until your symptoms
go away. These may be symptoms of CRS or neurologic problems.
EPKINLY can also cause other serious side effects,
- Infections. EPKINLY can cause serious infections
that may lead to death. Your healthcare provider will check you for
symptoms of infection before and during treatment. 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
- Low blood cell counts. 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 cell counts (neutropenia),
which can increase your risk for infection; low red blood
cell counts (anemia), which can cause tiredness and shortness
of breath; and low platelet counts (thrombocytopenia),
which can cause bruising or bleeding problems.
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 of your medical conditions, including if you:
- have an infection.
- are pregnant or plan to become pregnant. EPKINLY may harm your
unborn baby. Females who are able to become
pregnant: Your healthcare provider should do a pregnancy
test before you start treatment with EPKINLY. 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.
- are breastfeeding or plan to breastfeed. It is not known if
EPKINLY passes into your breast milk. Do not breastfeed during
treatment with EPKINLY and for 4 months after your last dose of
Tell your healthcare provider about all of the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
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 the Full Prescribing
Information and Medication Guide, including Important
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 www.abbvie.com/oncology and our Blood Cancer
Press Kit page.
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and solutions that solve serious health issues today and address
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1 U.S. Food and Drug Administration. Breakthrough
https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies. Accessed November
2 What is Lymphoma? Lymphoma Research Foundation.
https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed November 2023.
3 Ma S. Risk factors of follicular lymphoma. Expert Opin Med
Diagn. 2012;6:323-333. DOI: 10.1517/17530059.2012.686996.
4 Link BK, Day BM, Zhou X, 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.
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.
6 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: