Genmab to Submit sBLA to FDA for Epcoritamab Combo in Relapsed/Refractory Follicular Lymphoma
Genmab A/S, a leading international biotechnology company specializing in the development of antibody therapeutics for the treatment of cancer and other serious diseases, announced today its intention to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) in the first half of 2025. The filing will seek regulatory approval for a new combination regimen involving subcutaneous epcoritamab, a bispecific antibody, for use in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one prior systemic therapy.
This planned sBLA is supported by encouraging interim data from the ongoing Phase 3 EPCORE™ FL-1 trial, which is evaluating the efficacy and safety of epcoritamab when administered in combination with rituximab and lenalidomide—commonly known as the R2 regimen—compared to the R2 regimen alone. According to Genmab, the interim topline results demonstrated a statistically significant improvement in overall response rate (ORR), one of the study’s dual primary endpoints. The improvement in ORR, encompassing both complete and partial responses, was confirmed by an independent data monitoring committee (IDMC), which conducted a pre-planned interim analysis and validated the robustness of the findings with a p-value of less than 0.0001.
The clinical trial results suggest that the combination of epcoritamab with R2 may represent a meaningful advancement in the treatment landscape for patients with relapsed or refractory follicular lymphoma, a subtype of indolent non-Hodgkin lymphoma (NHL) that is typically slow-growing but considered incurable for many patients. While frontline therapies can often control the disease for a time, most patients eventually experience relapse, highlighting the critical need for novel, effective second-line or later treatment strategies.
Strong Clinical Foundation Underpins Regulatory Strategy
The decision to move forward with a supplemental submission to the FDA is strategically aligned with the goals of Project Frontrunner, a U.S. regulatory initiative that seeks to streamline the approval process for investigational therapies that demonstrate promising early clinical efficacy and safety. Genmab’s CEO, Jan van de Winkel, Ph.D., emphasized the importance of this regulatory milestone and its alignment with the company’s mission to bring transformative therapies to patients with unmet medical needs.
“We are pleased with the strength of the data that allows us to submit a supplemental Biologics License Application in accordance with the U.S. FDA’s Project Frontrunner, which supports our commitment to advance novel medicines to patients who need them,” said Dr. van de Winkel. “The interim topline results demonstrate the potential of this investigational epcoritamab combination regimen to treat relapsed or refractory follicular lymphoma patients. This milestone represents our commitment to the ongoing development of epcoritamab, with our partner AbbVie, and we look forward to seeing the full results from the study.”
Genmab and AbbVie are jointly developing epcoritamab as part of a broader oncology partnership focused on leveraging bispecific antibody technology to tackle some of the most challenging hematological malignancies. Epcoritamab is a subcutaneously administered bispecific antibody that simultaneously targets CD3 on T cells and CD20 on B cells, thereby directing the patient’s own immune system to recognize and kill malignant B cells. The drug has already garnered attention for its differentiated mechanism of action and its subcutaneous route of administration, which may offer convenience and reduced toxicity compared to traditional intravenous regimens.
No New Safety Concerns Observed in Combination Use
In addition to efficacy, the safety profile of epcoritamab in combination with R2 was closely monitored in the EPCORE FL-1 trial. Genmab reported that the safety findings were consistent with those previously observed for epcoritamab monotherapy and for the R2 regimen. Importantly, no new safety signals emerged in the combination arm, bolstering confidence in the therapeutic potential of the regimen.
The absence of new safety concerns is noteworthy, particularly in the context of combination therapy. While combining agents can sometimes result in overlapping toxicities or unexpected adverse events, the epcoritamab plus R2 regimen appears to maintain a manageable safety profile. This could be a crucial factor in securing regulatory approval and eventual adoption in clinical practice.
Full data from the EPCORE FL-1 trial, including secondary endpoints and detailed safety and efficacy analyses, are expected to be presented at a major upcoming medical congress later this year. In parallel, Genmab and AbbVie intend to engage with global regulatory agencies to discuss the next steps toward potential approvals in additional markets beyond the United States.
Epcoritamab’s Expanding Clinical Profile
Epcoritamab has already received Accelerated Approval from the FDA as a monotherapy for adults with relapsed or refractory follicular lymphoma who have undergone two or more prior lines of systemic therapy. This approval was based on earlier-phase clinical data demonstrating substantial antitumor activity and a favorable benefit-risk profile. However, the use of epcoritamab in combination with R2 for patients with FL who have received only one prior line of systemic treatment is not yet approved in the U.S., the European Union, or any other territory.
The upcoming sBLA represents a critical step toward expanding the clinical use of epcoritamab beyond the monotherapy setting. If approved, this new indication could offer an earlier treatment option for a broader population of FL patients, potentially improving long-term outcomes and quality of life.
Beyond follicular lymphoma, epcoritamab is being studied in several other B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL). The drug’s unique design and mode of action make it a versatile candidate for various hematologic cancers, and its development is a key focus within Genmab’s broader pipeline strategy.
Strategic Collaboration with AbbVie
Genmab’s collaboration with AbbVie, one of the world’s largest and most research-intensive biopharmaceutical companies, is central to the development and commercialization of epcoritamab. The two companies entered into a broad oncology collaboration in 2020, which includes the co-development of epcoritamab and other early-stage investigational antibodies.
Under the terms of the agreement, the companies share responsibilities for clinical development and commercialization efforts, with Genmab leading development in some indications and AbbVie in others. The collaboration is also designed to accelerate the global reach of epcoritamab, with both partners working in tandem to secure regulatory approvals and optimize market access.
The promising data from the EPCORE FL-1 trial and the forthcoming sBLA filing underscore the strength of this partnership and its potential to bring innovative immunotherapy options to patients with hematologic malignancies around the world.
With the planned sBLA submission in the first half of 2025, Genmab is positioning itself for a significant expansion of epcoritamab’s clinical utility in the follicular lymphoma treatment landscape. The results from the EPCORE FL-1 trial suggest that combining epcoritamab with rituximab and lenalidomide could offer a highly effective and well-tolerated treatment option for patients who have already undergone one line of systemic therapy.
As Genmab and AbbVie prepare to present the full data set and engage regulatory bodies in key global markets, anticipation is building for what could become a new standard of care for relapsed or refractory FL patients. This regulatory milestone reflects Genmab’s broader ambition to redefine cancer treatment through innovation in antibody engineering and translational research.
Should the FDA approve the sBLA, the epcoritamab plus R2 regimen would offer new hope to thousands of follicular lymphoma patients who face limited options after their initial treatment fails. It also reinforces the growing role of bispecific antibodies in reshaping the therapeutic paradigm in hematologic oncology.
