AbbVie and Genmab’s TEPKINLY approved by EC for advanced lymphoma

AbbVie (NYSE: ABBV) and Genmab (NASDAQ: GMAB) have announced that the European Commission (EC) has granted conditional marketing authorization for TEPKINLY (epcoritamab), a groundbreaking therapy for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) following two or more prior treatments. This approval marks a significant milestone as TEPKINLY becomes the first and only subcutaneous T-cell engaging bispecific antibody approved for treating both R/R follicular lymphoma and R/R diffuse large B-cell lymphoma (DLBCL) in the European Union (EU), the European Economic Area (EEA), and Northern Ireland.

Key Milestone in Lymphoma Treatment

TEPKINLY’s conditional approval represents a major step forward in addressing follicular lymphoma, a slow-growing non-Hodgkin’s lymphoma that arises from B-lymphocytes. As the second most common form of NHL, FL accounts for 20-30% of all cases. Despite its generally indolent progression, FL is deemed incurable with no standardized treatment options for patients at the third-line or later stages. These later stages often lead to shorter remissions and a higher likelihood of disease transformation into the more aggressive DLBCL.

Mariana Cota Stirner, M.D., Ph.D., Vice President and Therapeutic Area Head for Hematology at AbbVie, expressed enthusiasm about the approval. “The European approval of TEPKINLY for the treatment of follicular lymphoma after two or more prior treatments is yet another step forward in our aspiration to develop TEPKINLY as a potential core therapy across multiple B-cell malignancies,” Stirner stated. She highlighted the significance of expanding TEPKINLY’s use to follicular lymphoma, building on its initial approval for DLBCL, and reinforcing AbbVie’s commitment to enhancing cancer treatment.

Clinical Trial Insights

The conditional marketing authorization for TEPKINLY is supported by data from the Phase 1/2 EPCORE NHL-1 clinical trial. This open-label, multi-cohort, multicenter study evaluated TEPKINLY as a monotherapy in patients with R/R FL after two or more lines of prior systemic therapy. The trial included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, as well as those whose disease progressed within two years of initiating any first systemic therapy.

Results published in The Lancet Haematology demonstrated that TEPKINLY (n=128) achieved an overall response rate (ORR) of 83% and a complete response (CR) rate of 63%. The median duration of response was 21.4 months, with the duration of complete response (DOCR) not yet reached. These promising results underscore TEPKINLY’s potential in providing meaningful therapeutic benefits for patients with advanced follicular lymphoma.

Safety Profile and Optimization

In the study’s optimization cohort, 86 patients received the recommended 3-step-up doses for mitigating cytokine release syndrome (CRS). The optimized regimen revealed that 40% of patients experienced Grade 1 CRS and 9% experienced Grade 2 CRS, with no reports of Grade 3 or higher CRS. Notably, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed in this cohort.

The safety profile of TEPKINLY aligns with previous reports from the EPCORE NHL-1 DLBCL cohort. The most common adverse reactions (≥ 20%) included CRS, injection site reactions, fatigue, viral infections, neutropenia, musculoskeletal pain, pyrexia, and diarrhea. The most frequent serious adverse reaction was CRS (34%). Fourteen patients (3.7%) experienced fatal adverse reactions, including pneumonia and viral infections.

Epcoritamab’s Technological Edge

TEPKINLY, known as epcoritamab in the U.S., is developed using Genmab’s proprietary DuoBody technology. This technology enables the creation of bispecific antibodies designed to simultaneously engage two different targets. Epcoritamab binds to CD3 on T cells and CD20 on B cells, thereby directing T-cell-mediated killing of CD20+ cells. This innovative mechanism positions TEPKINLY as a significant advancement in the treatment of B-cell malignancies.

Ongoing and Future Developments

AbbVie and Genmab, co-developers of TEPKINLY, will continue to pursue regulatory approvals in additional international markets for both the R/R FL and R/R DLBCL indications. AbbVie will lead global commercialization efforts, while both companies will share responsibilities in the U.S. and Japan. Ongoing studies will further explore TEPKINLY’s efficacy as a monotherapy and in combination therapies for various hematologic malignancies.

Kate Rogers, CEO of the Follicular Lymphoma Foundation, remarked on the approval’s impact: “The approval of epcoritamab by the European Commission is a promising update for the lymphoma community. Given that relapsed or refractory follicular lymphoma is a very challenging form of cancer to treat, especially in later lines of therapy, it is critical that patients and physicians have additional options when it comes to treating this type of cancer.”