Genmab to Submit sBLA to FDA for Epcoritamab in Combination with Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma
Genmab A/S (Nasdaq: GMAB) has announced its plan to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) in the first half of 2025 for its investigational subcutaneous bispecific antibody, epcoritamab. The sBLA will seek approval for epcoritamab in combination with rituximab and lenalidomide—collectively known as the R2 regimen—for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one prior systemic therapy.
This regulatory submission marks a significant milestone in the development of epcoritamab, a next-generation T-cell engaging therapy designed to direct cytotoxic T cells to eliminate malignant B cells. Genmab’s submission is based on compelling topline results from its Phase 3 EPCORE™ FL-1 clinical trial, which evaluated the efficacy and safety of epcoritamab in combination with R2 versus the standard R2 regimen alone in patients with R/R FL.
Promising Phase 3 Results Support Submission
The decision to proceed with the sBLA was made following a pre-planned interim analysis of the EPCORE FL-1 study, conducted by an Independent Data Monitoring Committee (IDMC). According to Genmab, the trial successfully met one of its dual primary endpoints—overall response rate (ORR), which encompasses both complete responses and partial responses. The statistical significance of the finding (p-value < 0.0001) highlights the robust therapeutic potential of the epcoritamab-R2 combination.
Epcoritamab’s addition to the R2 regimen demonstrated enhanced anti-tumor activity without introducing new safety concerns. The observed safety profile was consistent with known data from prior studies of epcoritamab and the R2 regimen individually, as reflected in current prescribing information. No unexpected adverse events or safety signals were identified during the interim analysis.
While full results from the EPCORE FL-1 trial have yet to be publicly disclosed, Genmab stated that detailed data will be submitted for presentation at an upcoming scientific or medical congress later this year. The findings will also be shared with global health authorities as Genmab continues to pursue additional regulatory pathways beyond the United States.
Advancing Through Project Frontrunner
The sBLA will be submitted under the framework of the FDA’s Project Frontrunner, an initiative designed to support earlier access to promising oncology treatments in the relapsed/refractory setting. Project Frontrunner encourages companies to seek approval based on earlier lines of treatment when supported by strong clinical evidence, particularly in diseases where unmet medical needs persist.
“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 Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “The interim topline results demonstrate the potential of this investigational epcoritamab combination regimen to treat relapsed or refractory follicular lymphoma patients.”
Dr. van de Winkel emphasized the strategic importance of this development, noting that it represents a key milestone in Genmab’s broader clinical and commercial strategy for epcoritamab. “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.”
Addressing a Significant Clinical Need in Follicular Lymphoma
Follicular lymphoma, a slow-growing but typically incurable subtype of non-Hodgkin lymphoma, presents unique challenges for treatment. While many patients respond well to frontline therapies, relapse is common, and the effectiveness of subsequent treatments often diminishes with each line of therapy. As a result, there remains a substantial need for innovative and durable treatment options in the relapsed/refractory setting.
The R2 regimen—rituximab (an anti-CD20 monoclonal antibody) combined with lenalidomide (an immunomodulatory drug)—has become a widely used standard of care for patients with R/R FL. However, treatment resistance and disease progression are frequent concerns. Epcoritamab, with its unique bispecific mechanism of action, may enhance the immune system’s ability to recognize and destroy cancer cells when combined with R2.
Epcoritamab targets both CD3 on T cells and CD20 on malignant B cells, promoting targeted T-cell-mediated cytotoxicity. The subcutaneous administration route offers additional convenience and potentially improves the patient experience compared to intravenous therapies.
Current Regulatory Status of Epcoritamab
At present, the epcoritamab-R2 combination is investigational and has not received regulatory approval in any jurisdiction, including the U.S. or European Union. The safety and efficacy of epcoritamab as part of combination therapy in follicular lymphoma have not been established, and its use outside of clinical trials is not currently permitted.
However, epcoritamab is already available in the U.S. under the FDA’s Accelerated Approval pathway as a monotherapy for the treatment of adult patients with R/R FL who have received at least two prior lines of systemic therapy. This approval was based on response data from earlier clinical studies, and continued approval may be contingent on verification and description of clinical benefit in confirmatory trials.
The investigational use of epcoritamab in combination with R2, as evaluated in the EPCORE FL-1 study, represents a potential expansion of the product’s label to reach a broader population of patients earlier in their treatment journey.
Ongoing Collaboration with AbbVie
Genmab is co-developing epcoritamab in partnership with AbbVie, a global biopharmaceutical company. The two companies have entered into a collaboration to jointly develop and commercialize epcoritamab and explore its application across multiple B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL), among others.
The EPCORE clinical development program encompasses multiple trials evaluating epcoritamab as a monotherapy and in combination regimens, with the aim of establishing its role as a cornerstone therapy in hematologic oncology.
Genmab’s planned sBLA submission for epcoritamab plus R2 in R/R FL signals the company’s growing confidence in the product’s clinical profile and commercial potential. If approved, the combination therapy could offer a novel, effective treatment option for patients with limited alternatives after relapse.
As Genmab and AbbVie prepare for discussions with regulators, investors, and the broader scientific community, attention now turns to the full data set from the EPCORE FL-1 trial and its implications for the evolving treatment landscape in follicular lymphoma.
Should the FDA approve the new indication, it would represent a critical step forward in Genmab’s mission to transform the standard of care for patients with hematologic malignancies through targeted, immune-mediated therapies.
