Epkinly (Epcoritamab) Approved as First Bispecific Antibody for Most Common Non-Hodgkin’s Lymphoma

The US Food and Drug Administration (FDA) has granted approval to AbbVie and Genmab’s Epkinly (epcoritamab-bysp) as the first and only T-cell engaging bispecific antibody for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two or more lines of systemic therapy.

This includes DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma (HGBL).

The CD20xCD3 T-cell engager was approved under the FDA’s Accelerated Approval program based on response rate and durability of response. Under the program, confirmatory trials may be required for continued approval.

The drug is being touted as the best-in-class offering among CD20xCD3 bispecifics. This class of drugs includes Roche’s Lunsumio, which was the first to market having received approval late last year for follicular lymphoma, and Roche’s glofitamab in DLBCL, which is awaiting an FDA decision slated for July 1. Other drug candidates of this class include odronextamab from Regeneron and plamotamab being jointly developed by Johnson & Johnson and Xencor.

DLBCL is a type of aggressive, fast-growing non-Hodgkin’s lymphoma (NHL), a cancer that develops in the lymphatic system and affects B cells. DLBCL is the most common type of NHL, with an estimated 30,400 cases in the US in 2022 and 150,000 new cases each year worldwide.

Signs and symptoms of DLBCL can include swollen lymph nodes, fever, extreme night sweats, fatigue and weight loss.

Related: Interview About New Follicular Lymphoma Drug Lunsumio with Genentech’s Dr. Ginna Laport

CD20xCD3 bispecifics direct T cells to target malignant B cells that express CD20 on their surface.

“The FDA approval of Epkinly represents a new treatment for diffuse large B-cell lymphomas among patients who have relapsed or have refractory disease and are looking for a new medication,” said Meghan Gutierrez, CEO, Lymphoma Research Foundation in a statement.

DLBCL is conventionally treated with chemoimmunotherapy-based regimens. For patients with relapsed or refractory disease, several targeted therapies including T-cell-mediated treatments have recently emerged; however, single-agent and ready-available or off-the-shelf treatment options are limited.

Epkinly’s approval was based on results from the open-label, multicenter, single-arm Phase I/II EPCORE NHL-1 trial involving 148 patients with relapsed or refractory B-cell lymphoma.

The overall response rate (ORR), as determined by tumor shrinkage, was 61 percent among patients who had received a median of three prior lines of therapy, and 38 percent of patients achieved a complete response. Among responders, the estimated median duration of response was 15.6 months in a median follow-up of 9.8 months.

Compared to Phase I/II trial results for glofitamab, the Regeneron drug elicited a response in 51.6 percent of patients who had undergone a median of three prior lines of treatment, with 39.4 percent achieving a complete response.

In both trials, one-third of patients had previously received CAR-T therapy.

Epkinly appeared to have a better safety profile than its competitor glofitamab. One of the side effects of immunotherapies like bispecific antibodies is cytokine release syndrome (CRS), which is triggered by the overactivation of the immune system.

In their individual trials, Epkinly and glofitamab had CRS rates of 51 percent and 63 percent, respectively. Serious CRS cases occurred among 2.5 percent of patients who received Epkinly compared with 3.9 percent for glofitamab.

However, glofitamab demonstrated a longer duration of response, likely owing to its dosing strategy of administering the drug for a fixed period of time, according to Roche, as opposed to other meds in its class that are given until disease progression.

Epkinly may have another edge over glofitamab with respect to its easier route of administration. While Epkinly is administered subcutaneously, glofitamab is given intravenously.

Both AbbVie-Genmab and Roche are also looking to evaluate combination regimens for their CD20xCD3 agents in newly diagnosed DLBCL, which is an important arena for the drug class.

AbbVie and Genmab recently launched a Phase III EPCORE DLBCL-2 trial with Epkinly in combo with the standard R-CHOP regimen (three chemotherapy drugs given with a monoclonal antibody and a steroid) in newly diagnosed patients. Roche is planning to begin a similar Phase III study for glofitamab this year.

AbbVie and Genmab revealed Epkinly’s list price to be $37,500 per month, based on an average therapy duration of around nine months. The companies said the average price per month is expected to decrease after nine months as dosing becomes less frequent.