AbbVie 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). 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. 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.

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.

The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for "B-Cell Lymphomas" were recently updated (Version 2.2024 [1]) to add EPKINLY as a Category 2A, preferred recommendation for third-line and subsequent therapy for patients with FL. 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. 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.

EPKINLY can cause other serious side effects, including: · Infections that may lead to death. healthcare provider will check for signs and symptoms of infection before and during treatment and treat as needed if one develop an infection. One should receive medicines from healthcare provider before one start treatment to help prevent infection.

Tell healthcare provider right away if one develops 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. healthcare provider will check blood cell counts during treatment.

EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase risk for infection.