Genmab’s Tepkinly wins EC nod as first BsAb regimen for relapsed follicular lymphoma

Edited by Robert McTiernan··3 min read

The European Commission issued a marketing authorization for Tepkinly (epcoritamab) in combination with lenalidomide and rituximab (R²) for relapsed or refractory follicular lymphoma. The decision marks a meaningful shift in the EU treatment landscape: it is the first bispecific antibody-based regimen approved in Europe at the second-line setting for this indication, extending the class into an earlier and larger patient population than previously reached.

Genmab (Nasdaq: GMAB) and its collaborator AbbVie developed epcoritamab as an IgG1 CD20×CD3 bispecific antibody administered subcutaneously, using Genmab’s proprietary DuoBody platform. By simultaneously engaging CD3 on T cells and CD20 on malignant B cells, the molecule redirects cytotoxic T-cell activity toward tumor cells. The fixed-duration combination regimen — 12 cycles of epcoritamab alongside lenalidomide and rituximab — is designed to deliver deep, durable responses without conventional chemotherapy.

The approval is supported by the Phase III EPCORE FL-1 trial (NCT05409066), an open-label, randomized study comparing epcoritamab plus R² against R² alone in patients with R/R follicular lymphoma following at least one prior line of therapy. The dual primary endpoints were progression-free survival (PFS) and overall response rate (ORR) by Independent Review Committee assessment. Epcoritamab plus R² reduced the risk of disease progression or death by 79% compared with R² alone (HR 0.21, 95% CI: 0.13–0.33; p<0.0001). ORR reached 96% in the combination arm versus 81% for R² alone, and 74% of patients receiving epcoritamab plus R² achieved a complete response, compared with 43% in the control arm. Results were published in The Lancet in January 2026.

Follicular lymphoma is considered incurable, and outcomes tend to deteriorate with each successive relapse — a pattern that makes the depth of response in the second-line setting clinically relevant. Cytokine release syndrome, neutropenia, and pneumonia were among the notable adverse reactions; serious adverse reactions occurred in 44% of patients in the epcoritamab arm, a safety profile consistent with the bispecific antibody class.

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The EU approval positions epcoritamab earlier in the treatment pathway than the two other CD20×CD3 bispecifics currently authorized in Europe for follicular lymphoma. Roche’s mosunetuzumab (Lunsumio) and Regeneron’s odronextamab (Ordspono) are both conditionally approved in the EU, but for patients who have received at least two prior lines of systemic therapy — one line later than the epcoritamab plus R² indication. That line-of-therapy distinction is the primary clinical differentiator, giving epcoritamab access to a broader and earlier patient population.

The combination with lenalidomide and rituximab also differentiates epcoritamab from the monotherapy frameworks used by mosunetuzumab and odronextamab. Whether the combination’s superior efficacy reflects additive immunomodulatory activity from lenalidomide, or whether the R² backbone alone accounts for a portion of the benefit, remains a question the trial design — which compared epcoritamab plus R² against R² rather than against epcoritamab monotherapy — cannot fully resolve. As next-generation approaches in the CD20×CD3 bispecific class continue to emerge, epcoritamab’s combination data will serve as a benchmark.

Under the Genmab–AbbVie oncology collaboration established in 2020, AbbVie leads commercialization outside the US and Japan, with Genmab receiving tiered royalties on those sales. The EU approval therefore adds a commercially significant territory to AbbVie’s epcoritamab franchise, while reinforcing Genmab’s DuoBody platform as a productive source of approved medicines. Epcoritamab has now received regulatory authorization across more than 65 territories, including US FDA approval for R/R follicular lymphoma in combination with R² in November 2025.

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