Scottish Medicines Consortium (SMC) Approves First Subcutaneous Bispecific Treatment Option Tepkinly®▼(epcoritamab) for Adults with an Aggressive Form of Blood Cancer After Two or More Lines of Systemic Therapy

• For the first time, adults in Scotland with diffuse large B-cell lymphoma (DLBCL) whose cancer has returned or not responded to at least two prior treatments, will have access to a subcutaneous bispecific treatment option administered as an injection under the skin[1]^,[2].

• Epcoritamab is part of a new class of therapies called bispecific antibodies. Bispecific antibodies help the body’s immune system to attack and destroy cancerous cells[3].

• DLBCL is an aggressive blood cancer, with approximately 430 adults diagnosed with the disease in Scotland each year. For patients whose cancer has returned or has not responded to at least two prior treatments, prognosis is poor[4]^,[5]^,[6].

MAIDENHEAD, UK, [10^th June 2024] – AbbVie (NYSE: ABBV) today announced that the Scottish Medicines Consortium (SMC) has recommended Tepkinly^® (epcoritamab) as a treatment option for adults with DLBCL whose cancer has returned or not responded to at least two prior treatments¹. Following the recommendation by the National Institute for Health and Care Excellence (NICE) in March 2024, this means that epcoritamab is available for use within the NHS across the UK.

The SMC recommendation is based on the single-arm Phase 1/2 EPCORE NHL-1 trial data, in which subcutaneous epcoritamab monotherapy demonstrated responses in challenging-to-treat, relapsed or refractory (R/R) DLBCL patients who had received at least two prior treatments[7]. An overall response rate of 62% (n=86/139) was seen in this study, meaning 62% of participants’ blood cancer either went down by half (partial response) or showed no evidence of disease from tests and scans (complete response), and 39% (n=54/139) of patients achieved a complete response, where there is no evidence of disease from tests and scans^2,7,[8]^,[9].

Epcoritamab is the first and only subcutaneous T-cell engaging bispecific antibody licensed for the treatment of adult patients with R/R DLBCL after two or more lines of systemic therapy¹.

‘We are delighted that the SMC has made epcoritamab available to eligible people in Scotland living with this aggressive blood cancer. Epcoritamab is a bispecific antibody, administered as an injection under the skin, designed to recognise and attach to the cancer cells and immune cells, so that the body’s immune system can destroy them,’ said Blood Cancer UK’s Scotland Policy Officer, Josh Hill. ‘While most people go into remission after standard treatment, some people can see their cancer returning after each treatment option they try, leaving them feeling unsettled about what the future holds and what the next treatment option will entail.’

DLBCL is an aggressive blood cancer, with approximately 430 adults in Scotland, and nearly 5,500 adults across the UK being diagnosed each year ^5,6,[10]. For patients who have R/R DLBCL, meaning their cancer has returned or has not responded to at least two prior treatments, prognosis is poor⁴. There are few treatments available for this patient population, and these are typically administered intravenously, via a needle or tube inserted into a vein, in a hospital setting[11].

Epcoritamab is part of a new class of therapies called bispecific antibodies. Bispecific antibodies help the body’s immune system to attack and destroy cancerous cells. Epcoritamab is designed to simultaneously attach to two different cells, one immune T cell and one cancerous lymphoma cell, bringing them together so that the immune T cell is activated to destroy the cancerous lymphoma cell^2,3. While epcoritamab is given in a hospital setting, it is administered subcutaneously, meaning it is an injection under the skin².

‘Adults with DLBCL who have already been through two treatment options, but whose cancer has returned or has not responded, face limited alternative treatment options. It is important for physicians to have multiple treatment options, including products with different mechanisms of action and modes of administration, to provide patients with the choice of a treatment that is right for them. That’s why today’s approval is welcomed news for clinicians and eligible DLBCL patients.’ said Dr Angus Broom, Consultant Haematologist at the Western General Hospital in Edinburgh.

‘Epcoritamab is the first bispecific treatment option in this disease area that can be administered as an injection under the skin, in a hospital setting. This could allow patients to potentially be treated close to home, as this treatment can be delivered in a wider hospital setting rather than just specialist centres.’

In contrast to some existing therapeutic options, epcoritamab does not require cell collection and engineering². The treatment is given to eligible patients by a blood cancer specialist doctor or nurse as an injection under the skin, weekly for 12 weeks, then every other week for 24 weeks (12 injections), before continuing as one injection every 4 weeks until treatment is discontinued, either due to cancer progression or side effects². Eligible patients can start epcoritamab therapy after appropriate pre-medication has been administered and monitoring for adverse events is available². Patients stay in hospital for 24 hours after the first full dose to monitor for side effects².

In the Phase 1/2 NHL-1 clinical trial, epcoritamab prevented growth or spread of the cancer for an average of 15.6 months, and the patients lived for an average of 19.4 months from the start of epcoritamab therapy^2,7. The most common adverse reactions of any grade (≥20%) observed in the trial were cytokine release syndrome (CRS), fatigue, neutropenia, injection-site reactions, abdominal pain, pyrexia, nausea and diarrhoea².

‘Knowing that relapsed or refractory patients with DLBCL have limited treatment options, and the impact this may have on both their prognosis, mental wellbeing, and quality of life, drives us at AbbVie to advance standards of care. Today’s SMC decision is a result of our commitment to bring innovation to relapsed/refractory DLBCL patients and their loved ones.,’ said Rachael Millward, Medical Director, AbbVie UK.

-Ends-

UK media contact:

Rachael Pink

AbbVie UK

T: +44 (0)7816 180 570

E: rachael.pink@abbvie.com

NOTES TO EDITORS:

 

Glossary
Complete response rate of 39% (n=54/139)^2,7: The total number of people in the trial who experienced the disappearance of all evidence of lymphoma in the body from tests and scans after treatment^8,9.
Median duration of response of 15.6 months^2,7: The average length of time that a tumour continues to respond to treatment without the cancer growing or spreading[12].
Median overall survival of 19.4 months^2,7: The average time patients live for from the time they start treatment with epcoritamab¹².
Overall response rate of 62% (n=86/139)^2,7: The total number of people in the trial whose blood cancer either went down by half (partial response) or showed no evidence of disease from tests and scans (complete response)^8,9.
Refractory: Lymphoma that does not respond well to prior treatments, and patient does not go into remission¹⁰.
Relapse: Lymphoma that comes back after successful treatment and a period of remission¹⁰.

Remission: When there is no evidence of lymphoma in the body from tests and scans after treatment, and no symptoms¹⁰.

 

About DLBCL

Lymphoma is a blood cancer that causes tumours to form in the lymphatic system¹⁰. Lymphoma is divided into two main types: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL)[13]. DLBCL is a type of NHL, and makes up almost 30% of all cases of NHL globally[14]. There are approximately 5,500 new cases of DLBCL in the UK each year, with approximately 430 adults being diagnosed with the disease in Scotland^5,6,10. For around 700 of these patients in the UK whose cancer has returned or has not responded to at least two prior treatments, prognosis is poor^4,5,[15]. Patients with DLBCL typically have swollen lymph nodes in the neck, armpit or groin¹⁰.

About Tepkinly (epcoritamab)

Epcoritamab is recommended by the SMC as a subcutaneous injection to treat adults in Scotland with DLBCL that has come back (relapsed) or that did not respond to prior treatment (refractory), and who have received two or more treatments for their cancer¹. The treatment is given to eligible patients by a blood cancer specialist doctor or nurse as an injection under the skin, weekly for 12 weeks, then every other week for 24 weeks (12 injections), before continuing as one injection every 4 weeks until treatment is discontinued, either due to cancer progression or side effects².

 

Epcoritamab is an immunoglobulin G1 bispecific antibody created using Genmab’s proprietary DuoBody^® technology³. Genmab’s DuoBody^®-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types³. Epcoritamab is designed to simultaneously bind to cluster of differentiation (CD) 3 on T cells and CD20 on B cells, and induces T-cell-mediated killing of CD20+ cells³. CD20 is expressed on B cells, and is a clinically validated therapeutic target in many B-cell malignancies, including DLBCL[16]^,[17]. Epcoritamab was designed specifically for high-specificity binding³.

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 commercialisation.

About the EPCORE™ NHL-1 clinical trial^[18],[19]

EPCORE™ NHL-1 is a single-arm, open-label, multicentre, safety and preliminary efficacy trial of epcoritamab that includes a Phase 1 first-in-human dose escalation part; a Phase 2a expansion part; and a dose optimisation part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell NHL, including DLBCL. Data from the dose escalation part of the study, which determined the recommended Phase 2 dose, were published in September 2021. In the Phase 2 expansion part, additional patients were treated with epcoritamab to further explore the safety and efficacy of epcoritamab, in three cohorts of patients with different types of R/R B-cell NHL who had limited therapeutic options.

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. The most common adverse reactions of any grade (≥20%) observed in the trial were CRS (50.9%), fatigue (30.5%), neutropenia (30.5%), injection-site reactions (29.9%), pyrexia (23.4%), abdominal pain (23.4%), nausea (21.6%) and diarrhoea (21.0%). The most common Grade 3–4 adverse reactions (≥2%) were neutropenia (23.4%), anaemia (10.2%), thrombocytopenia (7.2%), pneumonia (6.0%), fatigue (3.0%), CRS (3.0%), febrile neutropenia (2.4%), oedema (2.4%) and hypophosphataemia (2.4%). The most common serious adverse reactions (≥2%) were CRS (31.1%), pneumonia (7.2%), upper respiratory tract infections (2.4%), febrile neutropenia (2.4%), immune effector cell-associated neurotoxicity syndrome (ICANS; 2.4%) and pyrexia (2.4%). Four patients (2.4%) experienced a fatal adverse reaction (ICANS in one patient [0.6%] and pneumonia in three patients [1.8%]).

Results from the Phase 2 expansion part of the study were published in December 2022.¹⁸ More information can be found at https://classic.clinicaltrials.gov/ct2/show/NCT03625037.

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About AbbVie in oncology

At AbbVie, we are committed to transforming standards of care for multiple blood cancers, while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials 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.

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 abbvie.co.uk. Follow @abbvieuk on X, formally known as Twitter, and YouTube.

References

Clicking the links below will take you to external websites that are not managed or owned by AbbVie.

 

[1] Scottish Medicines Consortium. epcoritamab (Tepkinly) - SMC2632. Available at: https://www.scottishmedicines.org.uk/medicines-advice/epcoritamab-tepkinly-smc2632-full/ [Last accessed: June 2024].

[2] Tepkinly. GB Summary of Product Characteristics.

[3] 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.

[4] Radford J, White E, Castro F, et al. Treatment Patterns and Outcomes in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Experience from a Single UK Centre. Blood. 2019;134(Suppl. 1):2917.

[5] Public Health Scotland. Cancer incidence in Scotland. Available from: https://publichealthscotland.scot/publications/cancer-incidence-in-scotland/cancer-incidence-in-scotland-to-december-2021/cancer-incidence-data-story/ [Last accessed: June 2024].

[6] Cancer Research UK. Diffuse large B cell lymphoma. Available from: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/diffuse-large-B-cell-lymphoma [Last accessed: June 2024].

[7] Jurczak W, Ghesquieres H, Karimi Y, et al. P1118: Longer follow-up from the pivotal epcore nhl-1 trial reaffirms subcutaneous epcoritamab induces deep, durable complete remissions in patients with relapsed/refractory large b-cell lymphoma. Hemasphere. 2023;7(Suppl):e081065c.

[8] Lymphoma Action. Remission. Available from: https://lymphoma-action.org.uk/about-lymphoma-treatment-lymphoma/remission#complete [Last accessed: June 2024].

[9] Cancer Research UK. What do clinical trial results mean? Available from: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/clinical-trial-results/what-do-clinical-trial-results-mean-0 [Last accessed: June 2024].

[10] Lymphoma Action. Diffuse large B-cell lymphoma. Available from: https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/diffuse-large-b-cell-lymphoma [Last accessed: June 2024].

[11] Blood Cancer UK. Diffuse large B-cell lymphoma (DLBCL) treatment and side effects. Available from: https://bloodcancer.org.uk/understanding-blood-cancer/lymphoma/diffuse-large-b-cell-lymphoma/dlbcl-treatment-side-effects/dlbcl-relapsed-and-refractory-treatment/ [Last accessed: June 2024].

[12] Delgado A, Guddati AK. Clinical endpoints in oncology – a primer. Am J Cancer Res. 2021;11(4):1121–1131.

[13] Lymphoma Out Loud. Lymphoma Signs and Symptoms. Available from: https://lymphomaoutloud.org/signs-symptoms [Last accessed: June 2024].

[14] Sehn LH, Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842–858.

[15] NICE. Resource impact template. Available from:

https://www.nice.org.uk/guidance/ta947/resources/resource-impact-template-excel-13309656877 [Last accessed: June 2024].

[16] Rafiq S, Butchar JP, Cheney C, et al. Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties. J Immunol. 2013;190(6):2702–2711.

[17] Singh V, Gupta D, Almasan A. Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response. J Cancer Sci Ther. 2015;7(11):347–358.

[18] Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023;41(12):2238–2247.

[19] ClinicalTrials.gov. First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma (EPCORE™ NHL-1). NCT03625037. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT03625037 [Last accessed: June 2024].