FDA Grants Priority Review to Epkinly for Follicular Lymphoma Based on Data From Phase I/II EPCORE NHL-1 Trial

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The FDA has granted Priority Review status to a supplemental Biologics License Application (sBLA) filed by Genmab A/S and AbbVie for Epkinly (epcoritamab-bysp) for the treatment of patients with relapsed or refractory (R/R) follicular lymphoma (FL) after prior treatment with two or more lines of therapy.¹ The subcutaneously administered, T-cell engaging, immunoglobulin G1 (IgG1)-bispecific antibody was granted Breakthrough Therapy Designation for this indication in November 2023.²

"Despite new treatment options, follicular lymphoma remains incurable and difficult to treat. Unfortunately, relapse is common and additional lines of treatment are needed," Mariana Cota Stirner, MD, PhD, AbbVie vice president, therapeutic area head for hematology, said in a press release. "Together with our partner Genmab, we are committed to further advancing epcoritamab as a core lymphoma therapy."¹

Epkinly concurrently attaches to the cluster of differentiation 3 (CD3) multimeric protein complex found on T cells, and cluster of differentiation 20 (CD20) found on B-cells. This action activates T cells to eliminate CD20 cells, which are prominent in patients with B-cell lymphomas. In June 2023, Epkinly was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a third-line and subsequent therapy for patients with diffuse large B-cell lymphoma (DLBCL) with disease progression following chimeric antigen receptor (CAR) T-cell therapy or transplant, or no intent for transplant after the development of aggressive disease from indolent lymphoma.³

The Priority Review designation was based on findings from the open-label, multi-center, safety and preliminary efficacy Phase I/II EPCORE NHL-1 trial. The three-part trial is comprised of a dose escalation portion, an expansion portion, and an optimization portion. Investigators analyzed Epkinly in patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (B-NHL), including FL, who were previously administered two or more lines of systemic therapy. The expansion portion enrolled additional patients to evaluate the drug’s safety and efficacy in three cohorts of patients with different types of R/R B-NHLs with limited therapeutic options.

The primary endpoint in the expansion part was overall response rate (ORR), with secondary efficacy endpoints that included duration of response (DOR), complete response (CR), duration of CR, progression-free survival, and time to response. Investigators also evaluated overall survival, time to next therapy, and rate of minimal residual disease negativity.

The results showed an 82% ORR in those administered Epkinly, which was greater than the protocol pre-specified efficacy threshold. Median DOR was not reached, requiring a longer follow-up, and the median number of prior lines of therapy was three. There were no new safety signals observed at the time of the analysis, with cytokine release found as the most common treatment-emergent adverse event at 66.4%.⁴

AbbVie and Genmab share commercial responsibilities for Epkinly in the United States and Japan. The companies announced they will seek additional international approvals for Epkinly for the investigational R/R FL indication and for the R/R DLBCL indication.¹

References

1. U.S. Food and Drug Administration (FDA) Grants Priority Review of Epcoritamab (EPKINLY®) for Difficult-to-Treat Relapsed or Refractory Follicular Lymphoma (FL). AbbVie. February 27, 2023. Accessed February 27, 2023. https://news.abbvie.com/2024-02-27-U-S-Food-and-Drug-Administration-FDA-Grants-Priority-Review-of-Epcoritamab-EPKINLY-R-for-Difficult-to-Treat-Relapsed-or-Refractory-Follicular-Lymphoma-FL

2. AbbVie announces US Food and Drug Administration and European Medicines Agency updates for epcoritamab (Epkinly/Tepkinly) for the treatment of relapsed/refractory follicular lymphoma. News release. AbbVie. November 27, 2023. Accessed February 27, 2023. https://news.abbvie.com/2023-11-27-AbbVie-Announces-U-S-Food-and-Drug-Administration-FDA-and-European-Medicines-Agency-EMA-Updates-for-Epcoritamab-EPKINLY-R-TEPKINLY-R-for-the-Treatment-of-Relapsed-Refractory-Follicular-Lymphoma

3. Genmab. Genmab Announces Epcoritamab Added to National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for ‘B-Cell Lymphomas’. News Release. June 22, 2023. Accessed February 27, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-announces-epcoritamab-added-national-comprehensive-cancer

4. AbbVie and Genmab announce positive topline results from phase 1/2 EPCORE NHL-1 trial evaluating epcoritamab (DuoBody-CD3xCD20) in patients with relapsed refractory follicular lymphoma. News release. AbbVie. June 28, 2023. Accessed February 27, 2023. https://news.abbvie.com/2023-06-27-AbbVie-and-Genmab-Announce-Positive-Topline-Results-from-Phase-1-2-EPCORE-TM-NHL-1-Trial-Evaluating-Epcoritamab-DuoBody-R-CD3xCD20-in-Patients-with-Relapsed-Refractory-Follicular-Lymphoma-FL