AbbVie Receives Positive CHMP Opinion for Epcoritamab (TEPKINLY®) for the Treatment of Adults with Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

• If approved, epcoritamab (TEPKINLY^®) will become the first and only subcutaneous bispecific antibody conditionally approved as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) DLBCL after two or more lines of systemic therapy
• The positive CHMP opinion is supported by results from the EPCORE™ NHL-1 Phase 1/2 trial evaluating the preliminary efficacy and safety of epcoritamab in patients with non-Hodgkin's lymphoma (NHL), including DLBCL
• DLBCL is an aggressive subtype of NHL and accounts for approximately 30 percent of all global cases

NORTH CHICAGO, Ill., July 21, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced 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 for epcoritamab (TEPKINLY^®) as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. The final European Commission decision on this indication for epcoritamab is anticipated later this year.

"As leaders in transforming standards of care, we strive to develop innovative medicines that can make an impact on patients facing aggressive blood cancers like DLBCL," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "We are pleased with the recent CHMP positive opinion for epcoritamab, as it represents an important step in our journey to develop a potential core therapy for people living with B-cell malignancies, such as DLBCL."

AbbVie's application for the approval of epcoritamab is supported by results from the pivotal EPCORE™ NHL-1 Phase 1/2 open-label, multi-center trial evaluating the preliminary efficacy and safety of epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL), including DLBCL. The primary endpoint of the study was overall response rate, as assessed by an independent review committee (63.1 percent).¹ The most common treatment-emergent adverse event was cytokine release syndrome.¹ Updated results were recently presented at multiple medical congresses.

"DLBCL is an aggressive and often treatment-resistant disease with limited therapeutic options for patients whose disease is refractory or who have experienced relapse after multiple lines of therapy," 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. "Subcutaneous epcoritamab could become a promising treatment option for the DLBCL community, and I look forward to the European Commission's final decision."

DLBCL is an aggressive type of cancer that develops in the lymphatic system.² It is the most common type of B-cell NHL worldwide and accounts for approximately 30 percent of all global cases.² Because NHL affects B-cell lymphocytes, the disease and its subtypes, including DLBCL, are classified as B-cell malignancies.²

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.

About the EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that includes a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a dose 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 (NHL), including large B-cell lymphoma (LBCL) and diffuse large B-cell lymphoma (DLBCL).³ Data from the dose escalation part of the study, which determined the recommended Phase 2 dose, were published in September 2021.⁴ In the Phase 2 expansion part, additional patients were treated with epcoritamab 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 had limited therapeutic options.³

The primary endpoint of the Phase 2 expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity. The most common treatment-emergent adverse events were cytokine release syndrome (49.7 percent; grade 1 or 2: 47.1 percent; grade 3: 2.5 percent), pyrexia (23.6 percent) and fatigue (22.9 percent). Results from the Phase 2 expansion part of the study were published in December 2022.¹ More information can be found on www.clinicaltrials.gov.

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody^® technology. 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.⁵ CD20 is expressed on B-cells and is a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.^6,7 

The safety and efficacy of epcoritamab remain under evaluation in the European Union (EU). The U.S. Food and Drug Administration (FDA) recently approved epcoritamab-bysp (EPKINLY™) in the United States, and it is indicated for the treatment of adult patients with R/R DLBCL, not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy. Epcoritamab-bysp 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.

Epcoritamab is not approved in the EU. If approved, epcoritamab will be marketed under the brand name TEPKINLY^® in all EU member states plus Liechtenstein, Norway, and Iceland. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets throughout the year.

EPKINLY™ (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

• 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 loss.

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, including:

• 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 generally unwell.
• 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 EPKINLY.

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 Warnings.

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 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, eye care, virology and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

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 2022 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 Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. JCO. Published online December 22, 2022:JCO.22.01725. doi:10.1200/JCO.22.01725.
² Sehn, Salles. "Diffuse Large B-Cell Lymphoma." N Engl J Med. 2021;384:842-858. DOI: 10.1056/NEJMra2027612.
³ First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma - clinicaltrials.gov. in. (n.d.). https://classic.clinicaltrials.gov/ct2/show/NCT03625037. Accessed July 5, 2023.
⁴ Hutchings M, Mous R, Roost Clausen M, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. The Lancet. Published Online September 8, 2021;volume 398, Issue 10306, P-1157-1169.
⁵ Engelberts 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.
⁶ Rafiq, Butchar, Cheney, et al. "Comparative Assessment of Clinically Utilized CD20-Directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK Cell, Monocyte, and Macrophage Properties." J. Immunol. 2013;190(6):2702-2711. DOI: 10.4049/jimmunol.1202588.
⁷ Singh, Gupta, Almasan. "Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response." J Cancer Sci Ther. 2015;7(11):347-358. DOI: 10.4172/1948-5956.1000373.

SOURCE AbbVie