Shots: 

• Recently, the EMA’s CHMP adopted a positive opinion by recommending conditional marketing authorization for AbbVie and Genmab’s Tepkinly for the treatment of R/R Follicular Lymphoma 

• Today at PharmaShots, we have Jacqueline Nielsen, Head of Hematologic Oncology Affairs at AbbVie, and Tahi Ahmadi, EVP and CMO at Genmab, shedding light on this conditional marketing authorization of Tepkinly in EU 

• Jacqueline and Tahi navigate the challenges with the approval and how the companies have strategized to overcome those obstacles 

Saurabh: Regarding the Phase 1/2 EPCORE® NHL-1 study, could you share the key findings that played a significant role in supporting the CHMP's decision?  

Jacqueline: The CHMP opinion for epcoritamab in follicular lymphoma (FL) was supported by overall and complete response data from the Phase 1/2 EPCORE® NHL-1 clinical trial in 128 patients with R/R FL treated with epcoritamab after two or more lines of systemic therapy. The study included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, patients who were refractory to last prior treatment, and patients whose disease progressed within two years of first systemic therapy. In the trial, the most common (≥10%) adverse reactions were cytokine release syndrome (CRS), injection site reactions, pyrexia, neutropenia, anemia, thrombocytopenia, diarrhea, nausea, headache, upper respiratory tract infection, pneumonia, and rash.   

An additional cohort of 86 patients evaluated an optimized step-up dosing (SUD) schedule to reduce the incidence and severity of CRS, which is an associated side effect from immune-engaging cancer treatments. Hospitalization was not mandatory in the optimization cohort. The incidence of CRS was 49% (42 of 86 patients; 9% were grade 2) and there were no grade 3 or higher CRS events in the optimization cohort. The EPCORE NHL-1 results, including results from the optimization cohort, were recently published in the Lancet Haematology. Additionally, data from the optimization cohort were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, selected to be a part of Best of ASCO® (July 19-20, Boston, MA), and were presented at the 2024 European Hematology Association (EHA) Congress. 

Saurabh: Patients receiving the present treatment option identify QoL as one unmet need. How does the use of subcutaneous administration for epcoritamab impact patient convenience and treatment adherence compared to other therapies?  

Jacqueline: Epcoritamab’s subcutaneous administration may provide eligible patients with a safe, effective and comfortable treatment option that enables accelerated treatment initiation across practice settings, including outpatient, to address high clinical need. Subcutaneous administration also allows more gradual increases and lower peaks in plasma cytokine levels than IV administration. Additionally, as an off-the-shelf treatment option, epcoritamab can be made available to treat patients at the moment of relapse. 

Saurabh: Can we discuss the collaboration between AbbVie and Genmab in developing and bringing epcoritamab to market? How does this partnership enhance the treatment options available for lymphoma patients?  

Jacqueline: AbbVie and Genmab are committed to developing epcoritamab as a core therapy for the treatment of multiple B-cell malignancies. Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies' broad oncology collaboration. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets. Both Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy and in combination across lines of therapy in a range of hematologic malignancies. 

Saurabh: Could you provide insights into the upcoming trials for epcoritamab? Specifically, which patient populations, geographic regions, and treatment settings will be the focus of these trials to further evaluate its efficacy and safety profile?  

Tahi: Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), and a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information. 

Saurabh: With the positive CHMP opinion, what additional challenges do you foresee in the process of bringing epcoritamab to market in the European Union, and how is AbbVie preparing to address these challenges? When might patients in the EU anticipate having access to epcoritamab?  

Tahi: AbbVie and Genmab are committed to working together to deliver epcoritamab to patients as quickly as possible. If approved, epcoritamab launch timing will vary based on market conditions. We cannot speculate on the timing of EU commercial availability at this time. 

Saurabh: Looking forward, how might the approval of epcoritamab impact the broader landscape of lymphoma treatment, particularly in terms of changing standards of care and improving patient outcomes?  

Tahi: AbbVie and Genmab are committed to developing epcoritamab as a core therapy for the treatment of multiple B-cell malignancies. If approved, epcoritamab (as the first and only bispecific antibody approved as a monotherapy in the EU to treat both R/R FL and R/R diffuse large B-cell lymphoma, or DLBCL, after two or more lines of prior therapy) will offer an accessible, off-the-shelf, T-cell engaging treatment option that enables accelerated treatment initiation across practice settings, including outpatient, to address high clinical need.  

Image Source: Canva 

About the Author: 

Jacqueline Nielsen 

Jacqueline Nielsen, PhD, is the Therapeutic Area Head of Hematologic Oncology Affairs at AbbVie. She has extensive experience in early drug development, laboratory assays and methodology, basic science, and translational research.   

Tahi Ahmadi 

Dr. Ahmadi joined Genmab in 2017 and became the Executive Vice President and Chief Medical Officer, Head of Experimental Medicines effective March 1, 2021. He holds an M.D. from the University of Cologne (Germany) and a Ph.D. from the University of Freiburg (Germany) and has expertise in translational research, strategic product development, global regulatory submissions and clinical development. Prior to joining Genmab, Dr. Ahmadi was head of experimental medicine and early development oncology at Janssen and a member of the Senior Leadership Team for Oncology. 

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