TEPKINLY® (epcoritamab) Gets Second EU Approval for Relapsed/Refractory Follicular Lymphoma in Adults

Genmab A/S announced that the European Commission (EC) has given conditional marketing authorization for TEPKINLY® (epcoritamab), a significant breakthrough in cancer treatment. This authorization allows TEPKINLY to be used as a monotherapy for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. This approval is noteworthy as TEPKINLY is the first and only subcutaneous T-cell engaging bispecific antibody approved for this specific patient population in the European Union (EU) and the European Economic Area (EEA) countries, which include Iceland, Liechtenstein, Norway, and Northern Ireland.

Jan van de Winkel, Ph.D., President and CEO of Genmab, expressed that this approval marks an important milestone for patients in need of a treatment with both meaningful efficacy and favorable safety. Genmab, in collaboration with AbbVie, aims to further explore the development of epcoritamab as a potential core therapy across various B-cell malignancies.

Follicular lymphoma (FL) is a typically slow-growing form of non-Hodgkin’s lymphoma (NHL) that originates from B-cell lymphocytes. It is the second most common form of NHL, representing 20-30 percent of all NHL cases and 10-20 percent of all lymphomas in the western world. FL is considered incurable, with no standard treatment for third-line or later FL, and patients who achieve remission often experience relapse.

The approval is based on data from the Phase 1/2 EPCORE® NHL-1 clinical trial, which evaluated TEPKINLY as monotherapy in patients with R/R FL after two or more lines of prior systemic therapy. The study involved patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, with a significant portion of patients also being refractory to their last prior treatment or having disease progression early in their treatment course. Results published in Lancet Haematology indicated that patients treated with TEPKINLY showed an overall response rate (ORR) of 83% and a complete response (CR) rate of 63%. The median duration of response was 21.4 months, with the duration of complete response not yet reached at a median follow-up of 16.2 months.

An optimization cohort within the study evaluated 86 patients with recommended doses for cytokine release syndrome (CRS) mitigation, showing that 40% experienced Grade 1 CRS and 9% experienced Grade 2 CRS. No Grade 3 or higher CRS or cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.

The safety profile of TEPKINLY was consistent with previous reports of epcoritamab monotherapy, with common adverse reactions including CRS, injection site reactions, fatigue, viral infections, neutropenia, musculoskeletal pain, fever, and diarrhea. Serious adverse reactions included CRS, with a small percentage of patients experiencing fatal adverse reactions.

Kate Rogers, CEO of the Follicular Lymphoma Foundation, highlighted that the approval offers a promising new option for patients and physicians dealing with the challenging nature of relapsed or refractory follicular lymphoma.

The EPCORE® NHL-1 trial was designed to evaluate the safety and preliminary efficacy of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL), including FL. The trial included dose escalation, expansion, and optimization parts, with the expansion part generating pivotal data for patients with FL and DLBCL.

Epcoritamab, developed using Genmab’s DuoBody® technology, binds to CD3 on T cells and CD20 on B cells, inducing T-cell-mediated killing of CD20+ cells. Currently approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU for certain lymphoma indications, epcoritamab is being co-developed by Genmab and AbbVie.

Both companies are pursuing additional regulatory approvals for epcoritamab across various hematologic malignancies, with ongoing Phase 3 trials evaluating its efficacy in different settings. Genmab aims to continue its innovative work in improving treatments for patients with serious diseases.