Genmab's Epkinly Achieves 79% Reduction in Disease Progression Risk in Phase III Follicular Lymphoma Trial
核心洞察
Genmab's bispecific antibody Epkinly combined with rituximab and lenalidomide demonstrated a 95.7% overall response rate and 79% progression-free survival in relapsed/refractory follicular lymphoma (搜索) patients.
The Phase III EPCORE FL-1 trial showed patients treated with the combination experienced a 79% reduction in risk of disease progression or death compared to standard therapy alone.
The FDA granted Priority Review and Breakthrough Therapy Designation for the combination, with a decision expected by November 30, 2025, potentially making it the first bispecific antibody combination for second-line follicular lymphoma (搜索) treatment.
Genmab's bispecific antibody Epkinly (epcoritamab) has achieved significant clinical milestones in treating relapsed or refractory follicular lymphoma (搜索), demonstrating a 79% reduction in risk of disease progression or death when combined with rituximab and lenalidomide in a Phase III trial. The results position the therapy as a potential game-changer for patients facing limited treatment options in this challenging disease setting.
Phase III Trial Results Show Strong Efficacy
The open-label EPCORE FL-1 trial (NCT05409066) evaluated 549 patients with relapsed or refractory follicular lymphoma (搜索), comparing Epkinly plus rituximab and lenalidomide (R2) against R2 alone. The combination therapy met both dual primary endpoints, achieving an overall response rate of 95.7% and progression-free survival of 79%.
"While therapeutic options exist for patients with relapsed or refractory follicular lymphoma (搜索), response rates tend to decline and durability diminishes with each subsequent line of treatment, which can increase the risk of the disease transforming into aggressive large-cell lymphoma," said Jan van de Winkel, PhD, CEO of Genmab.
The trial's dual primary endpoints were overall response rate and progression-free survival as assessed by independent review committee per Lugano criteria. Key secondary endpoints included complete response rates, overall survival, duration of response, and minimal residual disease negativity rates.
Regulatory Pathway and Market Positioning
The FDA has accepted Genmab's supplemental Biologics License Application for Epkinly plus R2 with Priority Review and Breakthrough Therapy Designation, setting a Prescription Drug User Fee Act target action date of November 30, 2025. If approved, Epkinly would become the first bispecific antibody combination regimen available in the United States as a second-line treatment option for patients with relapsed or refractory follicular lymphoma (搜索).
Epkinly was first approved in May 2023 for diffuse large B-cell lymphoma (搜索) after two or more lines of systemic therapies, and the FDA expanded its approval in June 2024 to include follicular lymphoma (搜索) patients after two or more lines of systemic therapy as a monotherapy.
Safety Profile and Mechanism of Action
The safety profile of the combination therapy remained consistent with the known safety profiles of each individual medicine, with no new safety signals identified. Epkinly is a bispecific antibody that targets CD3 (搜索) and CD20 (搜索), redirecting and activating T-cells to CD20-expressing cancer B-cells.
Disease Context and Unmet Need
Follicular lymphoma (搜索) represents the most common form of non-Hodgkin lymphoma (搜索), accounting for 20% to 30% of all cases. In the United States, approximately 15,000 people are diagnosed with follicular lymphoma annually, and over 25% of all cases are likely to transform into diffuse large B-cell lymphoma (搜索). The prevalence is approximately one in every 3,000 people, with a median diagnosis age between 60 and 65 years.
Competitive Landscape
The approval would give Epkinly a significant advantage over competing bispecific antibodies. Roche's Lunsumio (mosunetuzumab-axgb) was the first bispecific antibody approved in third-line follicular lymphoma (搜索) in December 2022, but its intravenous formulation and later-stage use could put it at a disadvantage compared to Epkinly's subcutaneous administration and potential second-line positioning.
According to market forecasts, Genmab and AbbVie (搜索)'s drug is projected to reach $2.32 billion in sales by 2031, compared to $999 million for Lunsumio. The full trial data from a pre-planned interim analysis will be presented at the upcoming American Society of Hematology meeting and will form the basis for regulatory submissions.
"The results from this trial, and the decision from the FDA to accept the sBLA for priority review, demonstrate the potential of this epcoritamab combination therapy to reshape the treatment landscape," concluded van de Winkel.