Genmab Announces Positive Regulatory Updates for Epcoritamab (EPKINLY®/TEPKINLY®) for the Treatment of Relapsed/Refractory Follicular Lymphoma

Rhea-AI Summary

Genmab A/S (GMAB) receives Breakthrough Therapy Designation from the FDA and regulatory application validation from the EMA for epcoritamab-bysp to treat relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. The FDA designation may expedite the development and review of the drug for serious or life-threatening diseases. The EMA's validation confirms that the application is complete and begins the scientific review process. The regulatory actions were supported by data from the EPCORE NHL-1 trial.

• U.S. Food and Drug Administration (FDA) grants Breakthrough Therapy Designation (BTD) for epcoritamab-bysp for the treatment of relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy
• European Medicines Agency (EMA) validates regulatory application for epcoritamab for the same indication
• The regulatory actions are supported by data from the phase 1/2 EPCORE™ NHL-1 trial

COPENHAGEN, Denmark--(BUSINESS WIRE)-- Genmab A/S (Nasdaq: GMAB) today announced regulatory 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. The U.S. FDA has granted Breakthrough Therapy Designation (BTD) to epcoritamab-bysp for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. BTD may expedite the development and review of investigational medicines by the U.S. FDA for serious or life-threatening diseases in cases where preliminary clinical evidence shows that a therapy may provide substantial improvements over available therapies.

Additionally, the EMA has validated a Type II variation application for epcoritamab for the same indication. EMA validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). If approved, R/R FL would become the second conditionally approved indication for epcoritamab in the European Union.

“Despite recent treatment advances in relapsed or refractory follicular lymphoma, a need still exists for more treatment options,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “We are encouraged by these recent decisions from the regulatory authorities, and we are hopeful that this may help accelerate the process of delivering epcoritamab to people living with this disease. We’re committed to working with AbbVie to explore the full potential of epcoritamab as a potential core therapy for patients with B-cell malignancies.”

These regulatory actions were supported by previously announced results from the phase 1/2 EPCORE NHL-1 clinical trial, an open-label, multi-center safety and preliminary efficacy study evaluating subcutaneous epcoritamab in 128 adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (NHL), including FL. Updated results from the R/R FL cohort of the EPCORE™ NHL-1 trial, including an optimized dosing schedule allowing for outpatient administration, will be presented at the upcoming 65^th Annual Meeting and Exposition of the American Society of Hematology (ASH) taking place December 9-12 in San Diego, California.

About Follicular Lymphoma (FL)

FL is typically an indolent, or slow-growing, form of non-Hodgkin's lymphoma (NHL) that arises from B-cell lymphocytes.ⁱ FL is the second most common form of NHL overall, accounting for 20 to 30 percent of all NHL cases, and representing 10 to 20 percent of all lymphomas in the Western world.^ii,iii Although FL is an indolent lymphoma, it is considered incurable with conventional therapy.^iv,v

About the Phase 1/2 EPCORE™ NHL-1 Trial

EPCORE™ NHL-1 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 patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (B-NHL), including FL. In the phase 2a 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 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 ORR as assessed by an IRC. Secondary efficacy endpoints included DOR, 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.

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.^vi

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. Use of epcoritamab in FL is not approved in the U.S. or in the EU. 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.

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 participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination with rituximab and lenalidomide in patients with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or 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

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 IMPORTANT

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.

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 guiding its unstoppable team to strive towards improving the lives of patients through innovative and differentiated antibody therapeutics. For more than 20 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational research and data sciences, which has resulted in a proprietary pipeline including bispecific T-cell engagers, next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates. To help develop and deliver novel antibody therapies to patients, Genmab has formed 20+ strategic partnerships with biotechnology and pharmaceutical companies. 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 locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.

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 What is Lymphoma? Lymphoma Research Foundation. https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed September 11, 2023.
ⁱⁱ Ma S. Risk factors of follicular lymphoma. Expert Opin Med Diagn. 2012;6:323-333. DOI: 10.1517/17530059.2012.686996.
ⁱⁱⁱ Luminari S, Bellei M, Biasoli I, et al. Follicular lymphoma—treatment and prognostic factors. Rev Bras Hematol Hemoter. 2012;34:54-59. DOI: 10.5581/1516-8484.20120015.
^iv 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.
^v 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.
^vi 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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David Freundel, Senior Director, Global Communications & Corporate Affairs

T: +1 609 430 2481m; E: dafr@genmab.com



Andrew Carlsen, Vice President, Head of Investor Relations

T: +45 3377 9558; E: acn@genmab.com

Source: Genmab A/S

FAQ

What is the significance of the Breakthrough Therapy Designation granted by the FDA to Genmab A/S (GMAB) for epcoritamab-bysp?

The FDA's Breakthrough Therapy Designation may expedite the development and review of epcoritamab-bysp for the treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

What does the regulatory application validation from the EMA mean for epcoritamab-bysp and Genmab A/S (GMAB)?

The EMA's validation confirms that the application for epcoritamab-bysp is complete and initiates the scientific review process by the EMA's Committee for Medicinal Products for Human Use (CHMP).

What trial data supported the regulatory actions for epcoritamab-bysp by Genmab A/S (GMAB)?

The regulatory actions were supported by data from the phase 1/2 EPCORE NHL-1 trial, an open-label, multi-center safety and preliminary efficacy study evaluating subcutaneous epcoritamab in adult patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin's lymphoma, including follicular lymphoma.

When will updated results from the R/R FL cohort of the EPCORE NHL-1 trial be presented?

Updated results from the R/R FL cohort of the EPCORE NHL-1 trial, including an optimized dosing schedule allowing for outpatient administration, will be presented at the upcoming 65th Annual Meeting and Exposition of the American Society of Hematology (ASH) taking place December 9-12 in San Diego, California.