Approval for the T-cell–engaging bispecific antibody came today from the FDA.
The FDA today approved the T-cell engaging bispecific antibody epcoritamab-bysp for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including those with DLBCL arising from indolent lymphoma or high-grade B-cell lymphoma.
Epcoritamab, to be marketed as Epkinly, will be available to patients who have received 2 or more lines of systemic therapy. It was approved under the FDA’s accelerated approval pathway, which will require verification of clinical benefit in confirmatory trials. The therapy is being jointly developed by AbbVie and Genmab.
DLBCL is a fast-growing type of non-Hodgkin lymphoma (NHL) and the most common type of the disease; it accounts for 30,400 new cases in the United States and 150,000 worldwide each year. Many new drug combinations have been developed for patients with R/R DLBCL, but as noted in a statement from AbbVie, single agent “off-the-shelf” treatments are less common.
"DLBCL is an aggressive cancer type that can rapidly progress and resist treatment. The FDA approval of [epcoritamab] represents a new treatment mechanism of action for third line DLBCL patients,” Thomas Hudson, MD, senior vice president, Research and Development, chief scientific officer AbbVie, said in the statement.
He highlighted epcoritamab’s status as a “nonchemotherapy, single-agent treatment for DLBCL.
"The approval is just the first step, with our partner Genmab, towards a shared goal of developing a core therapy for patients with B-cell malignances," he noted.
Epcoritamab is an immunoglobulin G 1 (IgG1) bispecific antibody created using Genmab's proprietary DuoBody technology, which induces potent cytotoxic activity of both CD4+ and CD8+ T cells to trigger an immune response toward target cell types. The technology is engineered to simultaneously bind to CD3 on T cells and to CD20 on B cells while inducing the destruction of CD20+ cells. The therapy is also being studied in follicular lymphoma and chronic lymphocytic leukemia with Richter’s syndrome.
“The approval of [epcoritamab] in the US is an incredibly important milestone for patients with relapsed or refractory DLBCL, who are in need of a new, innovative treatment option administered subcutaneously,” said Jan van de Winkel, PhD, CEO of Genmab in a statement.
Today’s approval was based on results from the phase 1/2 EPCORE NHL-1 clinical trial, which included an expansion cohort of 148 patients with CD20+ DLBCL, including 86% with DLBCL not otherwise specified, 27% with DLBCL transformed from indolent lymphoma, and 14% with high-grade B-cell lymphoma. Treatment with epcoritamab resulted in an overall response rate of 61%, a complete response rate of 38%, and duration of response of 15.6 months in heavily pretreated patients with R/R DLBCL.
"Patients with DLBCL who relapse or are refractory to currently available therapies have limited options. Generally, the prognosis for these patients is poor and management of this aggressive disease can be challenging," Tycel Philips, MD, City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, said in the statement.
"Epcoritamab is a subcutaneous bispecific antibody that offers an additional treatment option for this patient population," Philips said. “With this approval, patients who are in need of additional therapy may have the opportunity to receive epcoritamab after failure to respond or relapse after 2 or more systemic therapies."
The FDA will require a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. The most common (≥ 20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea.
Epkinly (epcoritamab-bysp) approved by US FDA as the first and only bispecific antibody to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). News release. PRNewswire. May 19, 2023. Accessed May 19, 2023. https://bit.ly/3BGQt9j