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Press Releases

Take a look at a selection of our recent media coverage:

Cladribine indication expansion to allow for earlier treatment in MS

4th April 2024

Cladribine tablets (brand name Mavenclad) have been granted a label extension by the Medicines and Healthcare products Regulatory Agency (MHRA) to expand access for additional patient populations with multiple sclerosis (MS), its manufacturer Merck has announced.

It is now indicated for the treatment of adult patients in Great Britain with relapsing forms of MS with active disease as defined by clinical or imaging features.

The expanded label means more newly diagnosed patients will be eligible for treatment with cladribine earlier in their disease course. Since 2017 it has been approved for use in patients with highly active relapsing MS as defined by clinical or imaging features.

Its latest approval makes cladribine the only short-course oral treatment for active relapsing MS available in Europe.

Cladribine tablets, which can be taken at home, are taken for a maximum of 20 treatment days in each of years 1 and 2 with no further treatment required in years 3 and 4.

This low administrative burden can offer advantages to a patient’s quality of life over other types of MS treatment, which can require drugs to be administered via regular self-injections, as an infusion in hospital, or as daily tablets, Merck said.

Speaking about the approval, Dr Wallace Brownlee, consultant neurologist and multiple sclerosis specialist, said: ‘The expansion of the label for cladribine tablets could improve patient outcomes and quality of life for many MS patients with active relapsing MS in Great Britain by allowing us to use cladribine tablets earlier in the treatment pathway.

‘This will be the first high-efficacy oral short-course treatment to be available for this patient group in Europe and could provide clinicians with an additional treatment option which also provides patients with treatment which has a low monitoring and administration burden.’

This approval by the MHRA follows a robust review of the current evidence around the benefit-risk profile of cladribine tablets for this patient group. The pre- and post-approval studies considered in the review included:

  • The CLARITY (Cladribine Tablets Treating MS Orally) study
  • The CLARITY extension study
  • The ORACLE MS (Oral Cladribine in Early MS) study
  • The ONWARD (Oral Cladribine Added ON to Interferon beta-1a in Patients with Active Relapsing Disease) study
  • The PREMIERE (Prospective Observational Long-term Safety Registry of Multiple Sclerosis) study

The review concluded that there is a favourable benefit-risk profile to warrant use in this wider population.

Dr Doina Ionescu, managing director of Merck Healthcare UK and Ireland, said: ‘We know from our long history of working in the field of MS that there is still an unmet need for many patients to have access to a high-efficacy oral treatment which can be used early in the course of the disease.

‘Since the NICE approval in 2017, cladribine tablets have treated globally over 80,000 patients which has been supported by data from both our pivotal studies and real-world evidence we have shared. More patients could benefit from cladribine tablets than before, so we look forward to applying for NHS reimbursement with urgency.’

Green light from MHRA and NICE for use of etrasimod in ulcerative colitis

14th March 2024

Etrasimod (brand name Velsipity) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) and recommended by the National Institute for Health and Care Excellence (NICE) for treating eligible patients with ulcerative colitis (UC).

It is approved for patients aged 16 years and older with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biological agent.

The recommended dose of etrasimod is one 2 mg tablet taken once daily with food for the first three days. After this, it can be taken each day with or without food.

The approval of etrasimod in the UK follows its marketing authorisation by the European Commission in February 2024 for the same indication.

This was the first time an oral advanced UC therapy had been approved for use in older adolescents.

Commenting on the recommendation, Helen Knight, director of medicines evaluation at NICE, said: ‘Severe ulcerative colitis is a debilitating lifelong condition; etrasimod provides a new convenient and effective treatment option that will make a positive difference for thousands of people.

‘I’m very pleased we have been able to publish our final guidance recommending the treatment on the day the MHRA granted it a licence. We are determined to continue getting the best care to patients fast.’

NICE has noted that just over 25,000 people in England are now eligible to receive the new treatment, which was evaluated using a simpler technology appraisal process.

As a result, the full final NICE guidance was available up to eight weeks faster than would have been the case under standard process.

Clinical efficacy of etrasimod

The MHRA and NICE approvals of etrasimod were based on results from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.

These randomised, double-blind, placebo-controlled trials involved 743 patients aged 16 years and over for whom standard treatment or other treatments did not work well enough or could not be used.

They evaluated the safety and efficacy of etrasimod 2 mg once daily on clinical remission.

The coprimary endpoints in ELEVATE UC 52 were the proportion of patients who achieved clinical remission at Week 12 (induction period) and Week 52 (maintenance period).

The primary endpoint for ELEVATE UC 12 was the proportion of patients in clinical remission at the end of the 12-week induction period.

Taken together, the results from the studies showed that, after 12 weeks of treatment, 26% (129/496) of those who received etrasimod had achieved clinical remission compared with 11% (27/247) of those who received the placebo.

ELEVATE UC 52 also found that 32% (88/274) of people taking etrasimod achieved clinical remission after 52 weeks compared with 7% (9/135) for those receiving the placebo.

Both studies also achieved all key secondary efficacy endpoints, with a favourable safety profile consistent with previous studies of etrasimod.

The most common side effects of the were found to be bradycardia, hypertension, urinary tract infection and lower respiratory tract infection.

NICE also noted that indirect comparisons suggest etrasimod is likely to work better than adalimumab and may be similarly effective to other usual treatments for moderately to severely active UC.

Momelotinib approved by MHRA for use in myelofibrosis patients with anaemia

9th February 2024

Momelotinib (brand name Omjjara) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) to treat adult myelofibrosis patients who have anaemia.

The Janus kinase (JAK) inhibitor is now indicated for the treatment of disease-related splenomegaly or symptoms in adult patients with moderate to severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis and who are Janus Kinase (JAK) inhibitor naive or have been treated with ruxolitinib.

The MHRA approval follows the positive opinion from the European Medicines Agency‘s Committee for Medicinal Products for Human Use in November 2023 for the same indication.

Momelotinib is taken in tablet form, once daily, at the same time each day.

Julian Beach, MHRA interim executive director, healthcare quality and access, said: ‘Myelofibrosis patients often rely on blood transfusions to counter their anaemia, but studies have shown that these transfusions are often linked to reduced quality of life and survival.

‘Keeping patients safe and enabling their access to high quality, safe and effective medical products are key priorities for us.

‘We’re assured that the appropriate regulatory standards for the approval of this medicine have been met.’

He added: ‘As with all products, we will keep the safety of this medicine under close review.’

Statistically significant response for momelotinib

This approval is supported by evidence from the randomised, double-blind phase 3 MOMENTUM trial involving 195 patients with myelofibrosis and anaemia, who had previously been treated with a JAK inhibitor.

The patients were given either 200mg momelotinib once daily, or 300mg of danazol twice daily, for 24 weeks.

Momelotinib demonstrated a statistically significant response with respect to constitutional symptoms, splenic response and transfusion independence compared to danazol at Week 24.

Some 25% of patients on momelotinib saw their symptoms reduce by at least half (against 9% on danazol) and 22% saw their enlarged spleen volume decrease by at least 35% (against 2% on danazol).

Momelotinib was also associated with favourable safety at Week 48 in a follow-up analysis.

The most common adverse reactions were diarrhoea, thrombocytopaenia, nausea, headache, dizziness, fatigue, asthenia, abdominal pain and cough.

Rezafungin approvals continue as MHRA gives go ahead for use in invasive candidiasis

2nd February 2024

Rezafungin (brand name Rezzayo) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of invasive candidiasis in adults.

This follows its approval by the European Commission in late December 2023 for the same indication.

An antimycotic, rezafungin selectively inhibits the fungal enzyme 1,3-β-D-glucan synthase, inhibiting formation of 1,3-β-D-glucan, an essential component of the fungal cell wall. This, in turn, results in rapid and concentration-dependent fungicidal activity in Candida species.

Rezafungin is administered once a week by a drip into the vein until at least 14 days after the last day Candida is found in the bloodstream.

Julian Beach, MHRA interim executive director, healthcare quality and access, said: ‘Keeping patients safe and enabling their access to high quality, safe and effective medical products are key priorities for us.

‘We’re assured that the appropriate regulatory standards for the approval of this medicine have been met.

‘As with all products, we will keep its safety under close review.’

Rezafungin demonstrates non-inferiority

The MHRA marketing authorisation was given to Napp Pharmaceuticals and is based on results from the randomised, double-blind, controlled phase 3 ReSTORE clinical trial.

This compared the efficacy and safety of intravenous rezafungin with intravenous caspofungin – the current standard of care – in patients with candidaemia and invasive candidiasis.

Chosen at random, 93 of the patients with invasive candidiasis were given a weekly dose of rezafungin and the other 94 were given a daily dose of caspofungin, for between two to four weeks. 

A total of 55 of the patients on rezafungin were cured at day 14, and 57 patients on caspofungin. Some 22 patients had died from any cause by day 30 on rezafungin, compared with 20 on caspofungin.

The trial therefore demonstrated statistical non-inferiority for rezafungin, dosed once weekly, when compared to caspofungin dosed once daily.

The most common side effects of rezafungin, which may affect more than 1 in 10 people, include hypokalaemia, diarrhoea and pyrexia.

Nivolumab-relatlimab approved by MHRA for advanced melanoma

3rd January 2024

The combined cancer treatment nivolumab-relatlimab (brand name Opdualag) has been granted marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA) for advanced melanoma.

The monoclonal antibody treatment manufactured by Bristol-Myers Squibb is now approved for adults and children from the age of 12 years.

Administered via a drip over 30 minutes every four weeks in a hospital under specialist medical supervision, nivolumab-relatlimab is continued for as long as clinical benefit is observed by the doctor, or until side effects become too severe.

Nivolumab attaches to the target protein PD 1 and relatlimab to LAG-3, blocking their actions and helping to increase T-cell activity against the melanoma.

This nivolumab-relatlimab approval was granted through Project Orbis, a global partnership between the MHRA, the Therapeutics Goods Administration in Australia, Health Canada, the Health Sciences Authority in Singapore, Swissmedic, Agência Nacional de Vigilância Sanitária in Brazil and Israel’s Ministry of Health, coordinated by the US Food and Drug Administration. 

This programme reviews and approves promising cancer drugs, helping patients to access treatments more quickly.

Nivolumab-relatlimab and progression-free survival

The Project Orbis decision on nivolumab-relatlimab was based on the results of a phase 2/3 randomised, double-blind clinical trial involving 714 patients with previously untreated advanced melanoma.

Patients were given either 480 mg nivolumab with 160 mg of relatlimab, or 480mg of nivolumab alone, every four weeks.

The primary endpoint was progression-free survival as assessed by blinded independent central review.

The researchers concluded that the combined nivolumab-relatlimab treatment was more effective at slowing the progression of the disease over those given nivolumab alone.

The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with nivolumab-relatlimab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab alone (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P=0.006 by the log-rank test).

Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with nivolumab-relatlimab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab alone.

Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients in the nivolumab-relatlimab group and in 9.7% of patients in the nivolumab group.

The most common adverse events experienced with nivolumab-relatlimab were tiredness; pain in muscles, bones and joints; skin rash (sometimes with blisters) and itching; decreased appetite; headache; diarrhoea; constipation; nausea; vomiting; stomach pain; fever; cough; difficulty breathing; underactive thyroid gland; skin colour change in patches (vitiligo); urinary tract infection; and decreased number of red and white blood cells.

In September 2023, nivolumab (brand name Opdivo) was approved by the European Commission for use as a monotherapy for the adjuvant treatment of stage IIB or IIC melanoma.

MHRA extends license of two cystic fibrosis drugs for children aged two to five

17th November 2023

The licence of the cystic fibrosis (CF) medicines ivacaftor-tezacaftor-elexacaftor (Kaftrio) and ivacaftor (Kalydeco) have been extended by the Medicines and Healthcare products Regulatory Agency (MHRA) to include children aged two to five years old.

These medicines, which are manufactured by Vertex Pharmaceuticals, are already authorised for use in the long-term treatment of CF with at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in adults and children aged six years and older.

F508del is the most common CF causing mutation.

Taken together, the CFTR modulator therapies work by interacting with certain abnormal CFTR proteins so they open more often to improve chloride movement in and out of cells.

They are available as sachets of granules to be mixed with 5ml of soft food and consumed immediately, just before or after a fat-containing meal or snack.

The license extension was based on the results of a study looking at this combination of drugs in patients aged 12 years and older in addition to data from a 24-week, phase 3 clinical study involving 75 patients aged 2-5 years old with a confirmed diagnosis of CF and at least one F508del mutation.

Participants continued their CF therapies, such as bronchodilators or inhaled antibiotics, but came off any CFTR modulator therapies other than the study drugs.

Safety was assessed by observing side effects to the medication and the effect of the treatment was assessed using the change in chloride concentrations in sweat.

Chloride concentrations in sweat reduced by 57.9 mmol/L over the course of the study in those aged two to five. This effect was comparable to the effect on sweat chloride in older children and adults where clinical efficacy and a comparable safety profile was demonstrated.

The most common side effects are a common cold, including sore throat and nasal congestion; headache, dizziness; diarrhoea; stomach pain; changes in the types of bacteria in the mucus; increased liver enzymes; and a rash.

Cystic fibrosis treatment under NICE review

Commenting on the license extension, John Stewart, national director for specialised commissioning at NHS England, said: ’Children as young as two years old with CF will now be eligible to receive the triple therapy if determined to be suitable by their treating clinician.

’We anticipate that as many as 600 children could benefit from this approval under the terms of the existing commercial agreement, and NHS England will publish an updated policy confirming this expansion in access and funding to coincide with stock arriving in England, which is anticipated in a few weeks.

’Patients, families and carers should be assured that NHS CF centres across the country have plans in place to ensure that all eligible children can be initiated on treatment while the NICE review of the CFTR modulators remains ongoing – meaning that all children eligible today can be confident about their long term access to these life-changing treatments.’

Earlier this month, the National Institute for Health and Care Excellence (NICE) published a first-stage draft recommendation for Kaftrio and two further CF treatments, which highlighted their clinical effectiveness.

However, it also stated that the ’most likely cost-effectiveness estimates’ were ’above the range that NICE considers an acceptable use of NHS resources. So they are not recommended’.

Commenting on the ’disappointing’ news, David Ramsden, CEO of Cystic Fibrosis Trust, said: ’It is important to emphasise that those already taking any of the modulator drugs are not affected by the NICE process because of the agreements already in place but this update creates uncertainty for those not yet on treatment.

’Vertex, NICE and the NHS must now urgently work together to find a solution to make these treatments available for all those who could potentially benefit. We must never return to a situation where people with CF die far too young, knowing there’s a treatment that could change that.’

The draft guidance is out for consultation until 24 November and a second evaluation meeting will be held on 14 December. Final publication is expected in March 2024.

World-first approval for curative exa-cel gene therapy in sickle cell disease

The first-of-its-kind gene-editing treatment exagamglogene autotemcel (exa-cel, brand name Casgevy) has been granted conditional marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of sickle cell disease and transfusion-dependent beta thalassemia (TDT).

Exa-cel is now approved for use in eligible patients aged 12 and over with sickle cell disease who have recurrent vaso-occlusive (VOC) crises, or TDT for whom a human leukocyte antigen-matched related hematopoietic stem cell donor is not available.

A genetically modified autologous CD34+ cell-enriched population, exa-cel contains human hematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 at the erythroid-specific enhancer region of the BCL11A gene.

The edited stem cells are then infused back into the patient to restore healthy haemoglobin production.

The innovative gene-editing tool CRISPR gained its inventors the Nobel Prize in 2020.

Professor Josu de la Fuente, professor of practice (cellular and gene therapy) at Imperial College London, and consultant haematologist at Imperial College Healthcare NHS Trust, said: ’This is a world-first and a significant moment for researchers, clinicians and, most of all, people with sickle cell disease and beta thalassaemia.

’These are inherited blood disorders which have a huge impact on people’s lives, including many people from our local community. This authorisation offers a new option for eligible patients who are waiting for innovative therapies.’

He added: ’I look forward to patients having access to this therapy as quickly as possible.’

The UK is the first country in the world to approve gene editing as a potential cure for these two inherited blood disorders. There are an estimated 2,000 patients eligible for Casgevy treatment across the country.

Life-long benefits in sickle cell disease

The MHRA approval was based on the results of two global clinical trials. Looking at exa-cel in both sickle cell disease and TDT, the trials met their respective primary outcome of becoming free from severe VOCs or transfusion independent for at least 12 consecutive months.

Once achieved, these benefits were potentially expected to be life-long.

The safety profile of 97 patients with SCD and TDT treated to date with Casgevy in these ongoing studies is generally consistent with the traditional treatments of myeloablative conditioning with busulfan and hematopoietic stem cell transplant.

Professor de la Fuente, who was also the chief national investigator of the UK arm and steering committee member of the two studies, said: ’I’m proud to have contributed to the development of the studies and be leading the UK arm. I am very grateful to my colleagues both at the Trust and the other centres involved in the trials and patient selection for their hard work, but most of all to the patients for their willingness to explore innovative therapies and their daily inspiration.’

Julian Beach, interim executive director of healthcare quality and access at the MHRA, added: ’Both sickle cell disease and beta thalassemia are painful, life-long conditions that in some cases can be fatal. To date, a bone marrow transplant – which must come from a closely matched donor and carries a risk of rejection – has been the only permanent treatment option.

He added: ’The MHRA will continue to closely monitor the safety and effectiveness of Casgevy, through real-world safety data and post-authorisation safety studies being carried out by the manufacturer.

’I would like to thank the patients with lived experiences who engaged with us as part of the assessment process and gave us valuable insight into their lives and the challenges of managing their condition.’

The manufacturer Vertex Pharmaceuticals is working closely with the National Institute for Health and Care Excellence to secure access for patients as soon as possible.

Exa-cel is also under review by the European Medicines Agency and other global regulators.

Anastrozole indication expanded by MHRA to include breast cancer prevention

7th November 2023

The aromatase inhibitor anastrozole has been approved by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) as a preventative treatment for breast cancer in postmenopausal women at moderate or high risk of developing the disease.

Previously authorised for the treatment of breast cancer in postmenopausal women, the drug has been used off-label for prevention and is now approved for this indication.

Anastrozole, which is off patent, is taken as a 1mg tablet, once a day for five years. It works by blocking the aromatase enzyme and reducing the amount of oestrogen that a patient’s body makes.

The most common side effects are hot flushes, feeling weak, pain or stiffness in the joints, arthritis, skin rash, nausea, headache, osteoporosis and depression.

According to Cancer Research UK, the entire five-year course of treatment now costs just £78, or around 4p a day.

Anastrozole was first recommended as a preventive option by the National Institute for Health and Care Excellence (NICE) in 2017, however, with the treatment being unlicensed in this use, uptake has remained low.

NHS England said around 289,000 women at moderate or high risk of breast cancer could be eligible for the drug. It estimated that if 25% of these women chose to take the drug, approximately 2,000 cases of breast cancer could potentially be prevented in England.

This would save around £15m in treatment costs, NHS England said.

NHS chief executive, Amanda Pritchard, said: ‘It’s fantastic that this vital risk-reducing option could now help thousands of women and their families avoid the distress of a breast cancer diagnosis.

‘Allowing more women to live healthier lives, free of breast cancer is truly remarkable, and we hope that licensing anastrozole for a new use today represents the first step to ensuring this risk-reducing option can be accessed by all who could benefit from it.’

The MHRA approval is based on the International Breast Cancer Intervention Study II (IBIS-II) study – an international, randomised double-blind, placebo-controlled trial.

The results showed a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, and fewer women developed breast cancer in the anastrozole group compared to the placebo group.

After a median follow-up of 131 months (IQR 105–156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio 0.51, 95% CI 0.39–0.66, p<0.0001). The reduction was larger in the first five years (35 vs 89, 0.39, 0.27–0.58, p<0.0001), but still significant after five years.

Anastrozole is the first medicine to be repurposed through the new Medicines Repurposing Programme, which looks at using existing medicines in new ways to benefit patients and the NHS. It is hosted by NHS England and supported by the Department of Health and Social Care, the MHRA, NICE and the National Institute for Health and Care Research.

The licensing work was undertaken by Accord Healthcare on a not-for-profit basis, after Accord Healthcare was selected through an open competitive process. The Medicines Repurposing Programme will now work with the MHRA and the British Generic Manufacturers Association to ensure other companies that make anastrozole adopt the new licensed indication.

Dr David Crosby, head of prevention and early detection at Cancer Research UK, said: ‘Repurposing therapeutic drugs that have already been shown to be safe for prevention is an area with a lot of potential.

‘More research will be key to finding more opportunities like this, to better understand who is at a high risk of getting cancer, and to help lower that risk.’

Adagrasib approved in the UK for NSCLC after earlier EU rejection

6th November 2023

Conditional marketing authorisation has been granted for adagrasib (brand name Krazati) by the UK‘s Medicines and Healthcare products Regulatory Agency (MHRA), its manufacturer Mirati Therapeutics has announced.

Adagrasib is a monotherapy indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRASG12C mutation who have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy.

The KRASG12C protein causes the cancer cells to grow out of control and it regenerates every 24-48 hours. Adagrasib is a highly selective and potent oral small-molecule inhibitor which is optimised to sustain target inhibition. attaches to the protein and stops it from working, which may slow down or stop the growth of the cancer. 

The drug is available in 200mg tablet form, with the recommended dose of three tablets taken at the same times twice a day.

The MHRA approval was based on the results of the KRYSTAL-1 open-label Phase 1/2 multiple-expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anti-cancer therapies in patients with advanced solid tumours harbouring the KRASG12C mutation.

In the trial, adagrasib was found to be a central nervous system (CNS) penetrant, which may be important given that CNS metastases frequently occur in NSCLC and lead to poor prognosis, Mirati Therapeutics said.

In a presentation at the recent European Society of Medical Oncology Congress, the company also shared data from the KRYSTAL-7 trial which demonstrated compelling efficacy and safety of adagrasib in combination with pembrolizumab in NSCLC.

Commenting on the approval, Dr Shobhit Baijal, consultant medical oncologist at The University Hospital Birmingham NHS Trust, said: ‘Some 14% of people living with NSCLC harbour the KRASG12C mutation yet there are limited targeted treatment options for patients with this devastating disease.

‘The expansion of treatment options for NSCLC benefits patients and clinicians alike. As someone intensively involved in the management of lung cancer patients, I look forward to Krazati being available for use in clinical practice.‘

NSCLC accounts for approximately 80-85% of the 43,000 lung cancer cases in the UK each year and an estimated 13-14% of these produce the KRASG12C protein. 

In July 2023, the European Medicines Agency issued a refusal of the conditional marketing authorisation for adagrasib after its ‘human medicines committee (CHMP) noted that comprehensive data for this medicine were not yet available and that there were uncertainties about how well the medicine worked‘.

The EMA concluded that Mirati Therapeutics did not provide evidence that the drug fulfils an unmet need for the type of approval it sought. The EMA therefore ‘could not justify making the medicine immediately available to patients while further data were still awaited‘.

Mirati Therapeutics disagreed with the opinion and intended to request a formal re-examination.

In the US, adagrasib was previously given accelerated approval by the FDA in December 2022.

Novel injectable bispecific antibody for advanced lymphoma receives EU and UK green light

23rd October 2023

The injectable bispecific antibody epcoritamab (brand name Tepkinly) has been granted conditional marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA), its manufacturer Abbvie has announced.

This follows its conditional marketing authorisation by the European Commission in late September 2023.

The conditional marketing authorisations recommend epcoritamab as a monotherapy for adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more systemic therapies.

Epcoritamab is the first and only off-the-shelf, subcutaneously administered CD3xCD20 T-cell-engaging bispecific antibody. It is designed to simultaneously bind to both the cluster of differentiation (CD)3 proteins on immune T cells and the CD20 proteins on cancerous B cells and activate the T cell to destroy the B cell.

Unlike existing therapeutic options for DLBCL, epcoritamab does not require cell collection and engineering before eligible patients can start treatment and it can be delivered in broader settings. It therefore has the potential for greater geographical accessibility and more timely administration.

Professor Chris Fox, professor of haematology at the University of Nottingham’s School of Medicine, and honorary consultant haematologist at Nottingham University Hospitals NHS Trust, UK, said: ‘Despite recent therapeutic advances, treatment options for patients with R/R DLBCL after two previous therapies are limited. For such patients living with this type of aggressive blood cancer, many experience disease progression and have poor prognosis.

‘As a novel bispecific antibody, given as a subcutaneous injection, epcoritamab offers a new treatment option for this difficult-to-treat patient group.’

Anna Sureda, head of clinical hematology department, Institut Català d’Oncologia – L’Hospitalet in Barcelona, Spain, said: ‘R/R 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.

‘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.’

Epcoritamab‘s EPCORE trial results

The conditional marketing authorisations are based on the results of the single-arm Phase 1/2 EPCORE NHL-1 trial, which investigated epcoritamab as monotherapy for 139 patients with R/R DLBCL after two or more lines of systemic therapy.

Phase 1 of the study looked at dose escalation, which determined the recommended phase 2 dose, and the phase 2 expansion treated additional patients to explore safety and efficacy. The primary endpoint was overall response rate determined by the 2014 Lugano criteria as assessed by an independent review committee.

Secondary 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.

Patients achieved an overall response rate of 61.9% (n=86/139) and a complete response rate of 39.6% (n=54/139).

The researchers also found that epcoritamab prevented the 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.

The trial results demonstrated a manageable safety profile, with cytokine release syndrome being the most common serious adverse event (31.1%), followed by pneumonia (7.2%), upper respiratory tract infections (2.4%), febrile neutropenia, 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%).

Further data from the trial are expected in due course.

‘An important step forward’

Commenting on the MHRA conditional marketing authorisation, Belinda Byrne, medical director at AbbVie UK, said: ‘AbbVie is committed to advancing care for people living with blood cancer. Today’s news is an important step forward in enabling us to provide this hard-to-treat patient group with an innovative subcutaneous treatment.

‘We are working with the NHS and relevant authorities to bring access to eligible patients and clinicians throughout the UK as quickly as possible.’

Epcoritamab is delivered to eligible patients by clinicians as a weekly subcutaneous injection for 12 weeks, then moves to every other week for 24 weeks (12 injections), before continuing as one injection every four weeks until treatment is discontinued due to cancer progression or side effects.

Epcoritamab is the first injectable bispecific antibody to be approved for use in DLBCL. It follows the recent MHRA approval and National Institute for Health and Care Excellence recommendation of glofitamab (brand name Columvi), a bispecific antibody administered via infusion.

Glofitamab also gained conditional marketing authorisation in the EU in July 2023.