Genmab Announces European Commission Approval of TEPKINLY® (epcoritamab) for Adults with Relapsed or Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL)
COPENHAGEN, Denmark; September 25, 2023 – Genmab A/S (Nasdaq: GMAB) announced today that the European Commission (EC) has granted conditional marketing authorization for TEPKINLY® (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. TEPKINLY is the first and only subcutaneous T-cell engaging bispecific antibody approved for the treatment of this patient population in the European Union (EU), as well as Liechtenstein, Norway and Iceland.
DLBCL is the most common type of B-cell non-Hodgkin’s lymphoma worldwide. While patients may have access to chemoimmunotherapy regimens to treat their disease, they face limited treatment options, with few readily available, off-the-shelf medicines, especially for those whose disease has relapsed or become refractory to prior treatments.i
“With TEPKINLY, people in Europe living with relapsed or refractory diffuse large B-cell lymphoma who are in need of additional treatment options now have a readily available, innovative therapeutic option for this aggressive cancer,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “Today’s approval underscores our commitment to bringing our bispecific antibody to more patients worldwide. We’re excited to continue working with our partner AbbVie to further explore epcoritamab as potential core therapy across B-cell malignancies.”
This conditional approval is supported by data from the pivotal EPCORE™ NHL-1 phase 1/2 open-label, multi-cohort, multi-center, single-arm trial evaluating the preliminary efficacy and safety of TEPKINLY in patients with R/R large B-cell lymphoma (LBCL), including its subtype DLBCL. In this study, DLBCL patients treated with TEPKINLY (n=139) achieved an overall response rate of 62 percent (n=86) and a complete response rate of 39 percent (n=54), with a median duration of response of 15.5 months (range: 9.7, not reached).
Results from the trial showed that TEPKINLY demonstrated a manageable safety profile across the LBCL patient cohort (n=167), which included the DLBCL patient population. The most common adverse reactions (= 20 percent) were cytokine release syndrome, fatigue, neutropenia, injection site reaction, musculoskeletal pain, abdominal pain, pyrexia, nausea and diarrhea.
“Relapsed or refractory DLBCL is an aggressive cancer and patients can face a difficult and emotional treatment journey. At this point in the journey, a patient may have had multiple lines of therapy and will already have experienced relapse,” said Anna Sureda, M.D., Ph.D., head of clinical hematology department, Institut Català d’Oncologia – L’Hospitalet, Barcelona, Spain. “This European Commission approval represents an important moment for the DLBCL patient community and brings with it a potential opportunity for effective disease management for a condition with limited available treatment options.”
Conditional marketing authorization is granted to medicines that address an unmet medical need, where the benefit of its immediate availability to patients outweighs the risk of limited data availability, and where confirmatory comprehensive data will need to be provided subsequently to maintain the marketing authorization.ii
Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets throughout the year.
About the EPCORE™ NHL-1 Trial
The median number of prior therapies was three (range: 2 to 11), with 30 percent receiving two prior therapies, 30 percent receiving three prior therapies, and 40 percent receiving four or more prior therapies. Eighteen percent had prior autologous hematopoietic stem cell transplantation (HSCT), and 39 percent had prior chimeric antigen receptor (CAR) T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29 percent of patients were refractory to CAR T-cell therapy.
The primary endpoint of the phase 2 expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity. More information can be found on www.clinicaltrials.gov.
About TEPKINLY (epcoritamab)
Epcoritamab-bysp (EPKINLYTM) was approved under accelerated approval in the United States in May 2023. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory trial(s). For more information, please see the Full Prescribing Information and Medication Guide, including Important Warnings.
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 three ongoing phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigators choice chemotherapy, a phase 3, trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R follicular lymphoma (FL) (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.
EU Indications and Important Safety Information about Tepkinly® q (epcoritamab)
Important Safety Information
Special warnings and precautions for use
Most CRS events occurred in Cycle 1 and were associated with the first full dose of Tepkinly. Administer prophylactic corticosteroids to mitigate the risk of CRS. Patients should be monitored for signs and symptoms of CRS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS. At the first signs or symptoms of CRS, institute treatment of supportive care with tocilizumab and/or corticosteroids as appropriate. Patients should be counselled on the signs and symptoms associated with CRS and patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Management of CRS may require either temporary delay or discontinuation of Tepkinly based on the severity of CRS.
Immune effector cell-associated neurotoxicity syndrome (ICANS)
Tumour Lysis Syndrome (TLS)
Fertility, pregnancy and lactation
Effects on ability to drive and use machines
Serious adverse reactions occurred in 52% of patients. The most frequent serious adverse reaction (= 10%) was cytokine release syndrome (31%). Seven patients (4.2%) experienced a fatal adverse reaction (pneumonia in 3 (1.8%) patients, viral infection in 3 (1.8%) patients and ICANS in 1 (0.6%) patient). Adverse reactions that led to discontinuation occurred in 6.6% of patients. Discontinuation of Tepkinly due to pneumonia occurred in 6 (3.6%) patients, viral infection in 3 (1.8%) patients, and CRS, ICANS, or fatigue in 1 (0.6%) patient each. Dose delays due to adverse reactions occurred in 32% of patients. Adverse reactions leading to dose delays (= 3%) were viral infections (9.6%), CRS (7.2%), neutropenia (4.8%), pyrexia (3.0%), and thrombocytopenia (3.0%).
This is not a complete summary of all safety information.
Established in 1999, Genmab is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.
Andrew Carlsen, Vice President, Head of Investor Relations
i Sehn, Salles. "Diffuse Large B-Cell Lymphoma." N Engl J Med. 2021;384:842-858. DOI: 10.1056/NEJMra2027612.
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