European Commission Grants Second Indication Approval for TEPKINLY® (epcoritamab) for the Treatment of Adults with Relapsed/Refractory Follicular Lymphoma
AbbVie (NYSE: ABBV) announced that the European Commission has granted conditional marketing authorization for TEPKINLY® (epcoritamab) as a monotherapy for treating adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of prior therapy. TEPKINLY is now the first and only subcutaneous T-cell engaging bispecific antibody approved to treat both R/R FL and R/R diffuse large B-cell lymphoma (DLBCL) in the European Union, European Economic Area countries, and Northern Ireland.
The approval is based on data from the Phase 1/2 EPCORE® NHL-1 clinical trial, which showed an overall response rate of 83% and a complete response rate of 63% in R/R FL patients treated with TEPKINLY. The median duration of response was 21.4 months. The safety profile was consistent with previous reports, with cytokine release syndrome being the most common adverse reaction.
AbbVie (NYSE: ABBV) ha annunciato che la Commissione Europea ha concesso l'autorizzazione all'immissione in commercio condizionata per TEPKINLY® (epcoritamab) come monoterapia per il trattamento di pazienti adulti affetti da linfoma folicolare (FL) in recidiva o refrattario (R/R) dopo due o più linee di trattamento precedenti. TEPKINLY è ora il primo e unico anticorpo bispecifico che ingaggia le cellule T, approvato per trattare sia il R/R FL che il linfoma diffuso a grandi cellule B (DLBCL) in Unione Europea, nei paesi dell'Area Economica Europea e in Irlanda del Nord.
L'approvazione si basa su dati provenienti dal trial clinico di fase 1/2 EPCORE® NHL-1, che ha mostrato un tasso di risposta globale dell'83% e un tasso di risposta completa del 63% nei pazienti con R/R FL trattati con TEPKINLY. La durata mediana della risposta è stata di 21,4 mesi. Il profilo di sicurezza è stato coerente con rapporti precedenti, con la sindrome da rilascio di citochine come reazione avversa più comune.
AbbVie (NYSE: ABBV) anunció que la Comisión Europea ha otorgado la autorización de comercialización condicional para TEPKINLY® (epcoritamab) como monoterapia para el tratamiento de pacientes adultos con linfoma folicular (FL) en recaída o refractario (R/R) tras dos o más líneas de terapia previa. TEPKINLY es ahora el primer y único anticuerpo bispecífico que involucra células T aprobado para tratar tanto el R/R FL como el linfoma difuso de células B grandes (DLBCL) en la Unión Europea, los países del Espacio Económico Europeo y en Irlanda del Norte.
La aprobación se basa en datos del ensayo clínico de fase 1/2 EPCORE® NHL-1, que mostró una tasa de respuesta global del 83% y una tasa de respuesta completa del 63% en pacientes con R/R FL tratados con TEPKINLY. La duración media de la respuesta fue de 21,4 meses. El perfil de seguridad fue consistente con informes anteriores, siendo el síndrome de liberación de citoquinas la reacción adversa más común.
AbbVie (NYSE: ABBV)는 유럽연합 집행위원회가 TEPKINLY® (epcoritamab)에 대해 두 차례 이상의 이전 치료 방법으로 치료를 받은 성인 환자의 재발 또는 불응성 (R/R) 모낭 림프종 (FL) 치료를 위한 단독 요법으로 조건부 마케팅 승인을 부여했다고 발표했습니다. TEPKINLY는 이제 유럽 연합, 유럽 경제 지역 국가 및 북아일랜드에서 R/R FL 및 R/R 미세 대세포 B 림프종 (DLBCL) 치료를 위해 승인된 최초이자 유일한 피하 T세포 결합 이중 특이성 항체입니다.
이번 승인은 TEPKINLY로 치료받은 R/R FL 환자에서 전체 반응률 83%와 완전 반응률 63%을 나타낸 1/2상 EPCORE® NHL-1 임상 시험 데이터를 기반으로 하고 있습니다. 반응의 중앙 지속 기간은 21.4개월이었습니다. 안전성 프로필은 이전 보고와 일치했으며, 사이토카인 방출 증후군이 가장 일반적인 부작용으로 나타났습니다.
AbbVie (NYSE: ABBV) a annoncé que la Commission Européenne a accordé une autorisation de mise sur le marché conditionnelle pour TEPKINLY® (epcoritamab) en tant que monothérapie pour le traitement des patients adultes atteints de lymphome folliculaire (FL) en rechute ou réfractaire (R/R) après deux ou plusieurs lignes de traitement antérieur. TEPKINLY est désormais le premier et unique anticorps bispécifique engageant les cellules T approuvé pour traiter à la fois le R/R FL et le lymphome diffus à grandes cellules B (DLBCL) dans l'Union Européenne, les pays de l'Espace Économique Européen et en Irlande du Nord.
L'approbation est basée sur des données de l'essai clinique de phase 1/2 EPCORE® NHL-1, qui a montré un taux de réponse global de 83 % et un taux de réponse complète de 63 % chez les patients R/R FL traités par TEPKINLY. La durée médiane de la réponse était de 21,4 mois. Le profil de sécurité était cohérent avec les rapports antérieurs, la syndrome de libération de cytokines étant l'effet indésirable le plus courant.
AbbVie (NYSE: ABBV) gab bekannt, dass die Europäische Kommission die bedingte Marktzulassung für TEPKINLY® (epcoritamab) als Monotherapie für die Behandlung von erwachsenen Patienten mit rückfälligem oder refraktärem (R/R) follikulärem Lymphom (FL) nach zwei oder mehreren vorherigen Therapielinien erteilt hat. TEPKINLY ist nun der erste und einzige subkutane, T-Zell-engagierende bispezifische Antikörper, der zur Behandlung von sowohl R/R FL als auch R/R diffus großzelligem B-Zell-Lymphom (DLBCL) in der Europäischen Union, den Ländern des Europäischen Wirtschaftsraums und Nordirland zugelassen ist.
Die Zulassung basiert auf Daten der Phase 1/2 EPCORE® NHL-1-Studie, die eine gesamtansprechrate von 83 % und eine vollständige Ansprechrate von 63 % bei R/R FL-Patienten zeigt, die mit TEPKINLY behandelt wurden. Die mediane Ansprechdauer betrug 21,4 Monate. Das Sicherheitsprofil war konsistent mit früheren Berichten, wobei das Zytokinfreisetzungssyndrom die häufigste unerwünschte Reaktion war.
- Conditional marketing authorization granted by European Commission for TEPKINLY in R/R follicular lymphoma
- First and only subcutaneous bispecific antibody approved for both R/R FL and R/R DLBCL in EU, EEA, and Northern Ireland
- High overall response rate of 83% and complete response rate of 63% in clinical trial
- Median duration of response of 21.4 months in R/R FL patients
- Conditional approval implies need for additional data to confirm long-term benefits
- Potential serious adverse reactions, including cytokine release syndrome (34% of patients)
- 3.7% of patients experienced fatal adverse reactions in the pooled safety population
Insights
This approval marks a significant advancement in the treatment of relapsed/refractory follicular lymphoma (FL). TEPKINLY's efficacy, with an 83% overall response rate and 63% complete response rate, is impressive for this difficult-to-treat patient population. The median duration of response of 21.4 months is particularly noteworthy, suggesting durable responses.
The optimized dosing regimen's reduced cytokine release syndrome (CRS) incidence is a important improvement, enhancing the therapy's safety profile. However, the 3.7% fatal adverse reaction rate warrants careful patient selection and monitoring. This approval provides a valuable option for FL patients who have exhausted other treatments, potentially improving outcomes in this incurable disease.
AbbVie's TEPKINLY approval for FL represents a significant market opportunity. As the first subcutaneous bispecific antibody approved for both FL and DLBCL in the EU, it has a unique positioning. With an estimated 13,000 FL cases annually in Western Europe and considering its approval for third-line treatment, TEPKINLY could capture a substantial market share.
The drug's efficacy and convenient administration route may drive adoption, potentially challenging existing therapies. However, its success will depend on pricing, reimbursement decisions and real-world performance. The conditional approval also means AbbVie must provide additional data, which could further strengthen TEPKINLY's market position if positive.
The EPCORE NHL-1 trial results are promising, demonstrating TEPKINLY's efficacy in a heavily pretreated population. The 63% complete response rate is particularly impressive for R/R FL. The optimization cohort's improved safety profile, with no Grade 3+ CRS or ICANS cases, addresses a key concern with T-cell engaging therapies.
However, the 3.7% fatal adverse reaction rate highlights the need for vigilant patient monitoring. Long-term follow-up data will be important to assess durability of responses and late-onset toxicities. Future studies comparing TEPKINLY to standard therapies and exploring combination strategies could further define its role in FL treatment algorithms.
- TEPKINLY (epcoritamab) is the first and only subcutaneous bispecific antibody conditionally approved as a monotherapy in the European Union to treat both relapsed or refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy
- FL is an incurable form of non-Hodgkin's lymphoma (NHL), with about 13,000 estimated cases in
Western Europe alone each year1
"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. First approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, its expansion into follicular lymphoma underscores its utility as a hematological cancer treatment," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "Together with our partner, Genmab, we are thrilled with today's approval which advances our commitment to elevating care for people living with cancer."
FL is typically a slow-growing form of non-Hodgkin's lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20
"The approval of epcoritamab by the European Commission is a promising update for the lymphoma community," said Kate Rogers, CEO of the Follicular Lymphoma Foundation. "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."
The conditional marketing authorization is supported by data from Phase 1/2 EPCORE® NHL-1 clinical trial: an open-label, multi-cohort, multicenter, single-arm trial that evaluated TEPKINLY as monotherapy in patients with R/R FL after two or more lines of prior systemic therapy. The study included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent (
The study included a planned separate optimization cohort, which evaluated 86 patients with the recommended 3-step-up doses for cytokine release syndrome (CRS) mitigation. Hospitalization was not mandatory in the cycle 1 optimization cohort. With the optimized regimen,
The safety profile of epcoritamab in the pivotal cohort was similar to reports of epcoritamab monotherapy in the pivotal EPCORE NHL-1 DLBCL cohort.6 In the pooled safety population (n=382), the most common adverse reactions (≥
About the Phase 1/2 EPCORE® NHL-1 Trial
EPCORE® NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (B-NHL), including FL. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The optimization part evaluates the potential for alternative step-up dosing regimens to help minimize overall rates and severity of cytokine release syndrome (CRS). The primary endpoint of the expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab.
More information can be found on www.clinicaltrials.gov (NCT03625037).
About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody® technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.
Epcoritamab (approved under the brand name EPKINLY® in the United States and TEPKINLY® in the European Union) has received regulatory approval in certain lymphoma indications in several countries.
Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies' oncology collaboration. The companies will share commercial responsibilities in the
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. Please visit clinicaltrials.gov for more information.
EU Indications and Important Safety Information about Tepkinly®▼(epcoritamab)
Indications
Tepkinly (epcoritamab) as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.
Tepkinly as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
Important Safety Information
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Special warnings and precautions for use
Cytokine release syndrome (CRS)
CRS, which may be life-threatening or fatal, occurred in patients receiving Tepkinly. The most common signs and symptoms of CRS include pyrexia, hypotension and hypoxia. Other signs and symptoms of CRS in more than two patients include chills, tachycardia, headache and dyspnoea.
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. 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. Patients with DLBCL 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.
Immune effector cell-associated neurotoxicity syndrome (ICANS)
ICANS, including a fatal event, have occurred in patients receiving Tepkinly. ICANS may manifest as aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral oedema. The majority of cases of ICANS occurred within Cycle 1 of Tepkinly treatment, however some occurred with delayed onset. Patients should be monitored for signs and symptoms of ICANS following Tepkinly administration. At the first signs or symptoms of ICANS treatment with corticosteroids and non-sedating-anti-seizure medicinal products should be instituted as appropriate. Patients should be counselled on the signs and symptoms of ICANS and that the onset of events may be delayed. Patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Tepkinly should be delayed or discontinued as recommended. Patients with DLBCL 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 ICANS.
Serious infections
Treatment with Tepkinly may lead to an increased risk of infections. Serious or fatal infections were observed in patients treated with Tepkinly in clinical studies. Administration of Tepkinly should be avoided in patients with clinically significant active systemic infections. As appropriate, prophylactic antimicrobials should be administered prior to and during treatment with Tepkinly. Patients should be monitored for signs and symptoms of infection, before and after Tepkinly administration, and treated appropriately. In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines.
Tumour Lysis Syndrome (TLS)
TLS has been reported in patients receiving Tepkinly. Patients at an increased risk for TLS are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs or symptoms of TLS, especially patients with high tumour burden or rapidly proliferative tumours, and patients with reduced renal function. Patients should be monitored for blood chemistries and abnormalities should be managed promptly.
Tumour flare
Tumour flare has been reported in patients treated with Tepkinly. Manifestations could include localized pain and swelling. Consistent with the mechanism of action of Tepkinly, tumour flare is likely due to the influx of T-cells into tumour sites following Tepkinly administration. There are no specific risk factors for tumour flare that have been identified; however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumour flare in patients with bulky tumours located in close proximity to airways and/or a vital organ. Patients treated with Tepkinly should be monitored and evaluated for tumour flare at critical anatomical sites.
CD20-negative disease
There are limited data available on patients with CD20-negative DLBCL and patients with CD20-negative FL treated with Tepkinly, and it is possible that patients with CD20-negative DLBCL and CD20-negative FL may have less benefit compared to patients with CD20-positive DLBCL and patients with CD20-postitive FL, respectively. The potential risks and benefits associated with treatment of patients with CD20-negative DLBCL and FL with Tepkinly should be considered.
Immunisation
Live and/or live-attenuated vaccines should not be given during Tepkinly therapy. Studies have not been conducted in patients who received live vaccines.
Fertility, pregnancy and lactation
Tepkinly is not recommended during pregnancy and in women of childbearing potential not using contraception.
Effects on ability to drive and use machines
Tepkinly has minor influence on the ability to drive and use machines. Due to the potential for ICANS, patients should be advised to exercise caution while (or avoid if symptomatic) driving, cycling or using heavy or potentially dangerous machines.
Undesirable effects
Summary of the safety profile
The safety of Tepkinly was evaluated in 382 patients with relapsed or refractory large B-cell lymphoma (N=167), FL (N=129) and FL (3-step step-up dose schedule N=86) after two or more lines of systemic therapy and included all the patients who enrolled to the 48 mg dose and received at least one dose of TEPKINLY. The most common adverse reactions (≥
Serious adverse reactions occurred in
Dose delays due to adverse reactions occurred in
This is not a complete summary of all safety information.
See Tepkinly® full Summary of Product Characteristics (SmPC) at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, and bi-specific and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.
Today, our expansive oncology portfolio is comprised of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit us at http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
AbbVie Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
1 Kanas G, Ge W, Quek RGW, et al. Leukemia & Lymphoma. 2022;63(1):54-63 |
2 Lymphoma Research Foundation official website. https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed February 2024. |
3 Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822-832. doi: 10.3324/haematol.2022.281421. |
4 Rivas-Delgado A, Magnano L, Moreno-Velázquez M, et al. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br J Haematol. 2018;184(5):753-759. doi:10.1111/bjh.15708. |
5 Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625. |
6 Linton Kim, Vitolo Umberto, Jurczak Wojciech, et al. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol. 2024. https://doi.org/10.1016/ S2352-3026(24)00166-2. |
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FAQ
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