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1st February 2024
AbbVie’s bispecific antibody treatment epcoritamab (brand name Tepkinly) has been recommended by the National Institute for Health and Care Excellence (NICE) to treat relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) – the first bispecific to be given as a subcutaneous injection.
DLBCL is an aggressive blood cancer with nearly 5,500 new diagnoses in the UK each year, and poor prognosis for some 700 of these patients who have R/R DLBCL.
The new recommendation means adults with DLBCL whose cancer has returned or has not responded to at least two previous treatments, and who have previously had polatuzumab vedotin or it is contraindicated or not tolerated, will have access to epcoritamab subcutaneous bispecific treatment option administered in a hospital setting.
This follows the granting of conditional marketing authorisation by the UK’s Medicines and Healthcare products Regulatory Agency in October 2023 and by the European Commission in late September 2023.
In contrast to some existing therapeutic options, which are administered intravenously, epcoritamab does not require cell collection and engineering.
The treatment is given by a blood cancer specialist doctor or nurse to eligible patients weekly for 12 weeks, then every other week for 24 weeks (12 injections), before continuing as one injection every four weeks until treatment is discontinued, either due to cancer progression or side effects.
Eligible patients can start epcoritamab therapy after appropriate premedication has been administered and monitoring for adverse events is available. Patients stay in hospital for 24 hours after the first full dose to monitor for side effects.
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, said: ‘Despite recent therapeutic advances, treatment options for this hard-to-treat group of patients have been limited.
‘This can mean many patients do not have suitably effective treatment options, resulting in a poor prognosis. [This] decision by NICE on epcoritamab gives patients and clinicians an additional choice of administration option, which may help to support capacity planning within lymphoma services.’
He added: ’The decision by NICE will be welcomed by both patients and the clinical community.’
The NICE recommendation is based on data from the single-arm, open-label, multicentre safety and preliminary efficacy phase 1/2 EPCORE NHL-1 trial,
The trial demonstrated a 62% (n=86/139) overall response rate, meaning 62% of participants’ blood cancer either went down by half (partial response) or showed no evidence of disease from tests and scans (a complete response).
The complete response rate was 39% (n=54/139), meaning there was no evidence of disease from tests and scans in 39% of these hard-to-treat patients, who on average had already been through three types of treatment before starting the trial.
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.
The most common adverse reactions of any grade (≥20%) observed in the trial were cytokine release syndrome (50.9%), fatigue (30.5%), neutropenia (30.5%), injection-site reactions (29.9%), abdominal pain (23.4%), pyrexia (23.4%), nausea (21.6%) and diarrhoea (21.0%).
Commenting on the NICE recommendation, Rincy George, policy officer at Blood Cancer UK, said: ‘Like many that experience blood cancer, people with relapsed or refractory DLBCL experience anxiety around the prospect of not responding to treatment or the cancer once again returning.
’Today’s decision from NICE approving epcoritamab for eligible patients for use on the NHS in England and Wales is a welcome step for many.’
30th October 2023
The biologic treatment secukinumab (brand name Cosentyx) has been recommended in final draft guidance by the National Institute for Health and Care Excellence (NICE) for hidradenitis suppurativa (HS), its manufacturer Novartis has announced.
The first biologic treatment to be recommended for the condition since adalimumab in 2016, secukinumab is suitable for adults in England and Wales with active moderate to severe HS, where there has been an inadequate response to conventional systemic therapy and where adalimumab is not suitable, did not work or has stopped working.
Commenting on the development, Dr John Ingram, clinical reader and consultant dermatologist at Cardiff University, said: ‘HS is an undertreated disease that causes substantial physical and emotional distress to those who live with it. Until now, there has only been one approved biologic treatment for HS, and many patients can lose response.
‘[The] NICE decision provides physicians with a second treatment option that has shown significant clinical benefits in the domains that matter most to patients, including swift improvement in quality of life and skin pain.’
The NICE recommendation is based on the results of the SUNSHINE and SUNRISE multicentre, randomised, double-blind, placebo-controlled, parallel group trials, which formed the largest phase 3 programme in HS to date.
Across the two trials, 1,084 participants were randomly assigned (1:1:1) to receive subcutaneous secukinumab 300 mg every two weeks or every four weeks, or subcutaneous placebo.
The treatment response rates in patients randomised to secukinumab continued to improve beyond the primary endpoint analysis at Week 16 to more than 55% of patients achieving a Hidradenitis Suppurativa Clinical Response at Week 52.
Approximately 50% of patients randomised to secukinumab had a reduction in HS-related pain at Week 52. Safety findings were consistent with the generally well-tolerated safety profile of secukinumab in its approved dermatological and rheumatological licensed indications and are further supported by data from eight years of real-world use.
The authors concluded that ‘when given every two weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment’.
Through an agreement between Novartis and NHS England, eligible people living with HS to obtain immediate access to secukinumab through the interim Innovative Medicines Fund, which provides funding to accelerate NICE-recommended non-cancer medicines into the NHS.
In addition, the New Treatment Fund in Wales will enable early access to secukinumab for eligible patients in Wales.
Secukinumab, an interleukin-17A inhibitor, was approved in the EU and UK in 2015 for treating moderate to severe plaque psoriasis in adults. The license was extended to include children and young people aged six to 17 in the EU in 2020 and UK in 2021.
Marie-Andrée Gamache, country president, Novartis Innovative Medicines UK and Ireland, said: ‘[The] NICE recommendation is an example of how we are reimagining medicine to improve the lives of people with hard-to-treat inflammatory conditions and has been made possible through effective collaboration with NICE and NHS England.
‘Since its first approval in the UK in 2015, secukinumab has been used to treat over one million patients worldwide and could now provide another option for eligible patients in England and Wales who continue to struggle with the painful and debilitating symptoms of HS.’
19th October 2023
The NHS will fast-track the bispecific antibody glofitamab (brand name Columvi) for treating relapsed or refractory (R/R) diffuse large B‑cell lymphoma (DLBCL) in adults after two or more systemic treatments following its recommendation by the National Institute for Health and Care Excellence (NICE).
Set to be made available in England ‘within weeks‘, glofitamab is the first off-the-shelf CD20xCD3 T-cell engaging bispecific antibody. Administered as an intravenous infusion, it works by encouraging healthy immune cells in the body to destroy the cancer cells.
While current DLBCL treatments such as CAR T therapies are provided in specialist centres across England, glofitamab can be offered at more cancer treatment sites across the country, improving timely access. It is thought that more than 700 people in England could benefit from the treatment.
NHS England’s Cancer Drug’s Fund Lead, Professor Peter Clark, said: ’The approval of this drug is great news for people living with an advanced and aggressive form of blood cancer, who are set to benefit from this new treatment.
’Not only does it provide a potentially life-saving option for patients who may have not responded to CAR T therapy, it is also an alternative for some CAR T eligible patients who choose instead to have glofitamab closer to home.
’This is the latest in a long list of cutting-edge drugs available on the NHS to help people with cancer live a longer and better-quality life.’
Helen Knight, director of medicines evaluation at NICE, added: ‘We are committed to getting the best care to patients fast while ensuring good value for the taxpayer.
‘Advanced B-cell lymphoma is an aggressive form of blood cancer and can progress quickly. The sooner people can access the best treatment for them, the better chance they have of living for longer and improving their quality of life.
‘This is why it is such good news that our independent committee has found that glofitamab is clinically and cost effective for treating people with this advanced form of cancer, and we welcome the news that NHS England will make this available to patients quickly.‘
The NICE recommendation coincides with glofitamab receiving its license by the Medicines and Healthcare products Regulatory Agency and is based on the positive results obtained from the Phase 1/2 NP30179 study.
Of the 154 participants who received treatment, 39% (95% confidence interval [CI], 32 to 48) had a complete response at a median follow-up of 12.6 months.
The majority (78%) of complete responses were ongoing at 12 months. The 12-month progression-free survival was 37% (95% CI, 28 to 46).
The most common adverse event was cytokine release syndrome (CRS) (63%). Adverse events of grade 3 or higher occurred in 62% of the patients, with grade 3 or higher CRS in 4% and grade 3 or higher neurologic events in 3%. Discontinuation of glofitamab due to adverse events occurred in 9% of the patients.
Referring to the rollout of bispecific antibodies as a breakthrough for patients with lymphoma, Dr Wendy Osborne, an NHS consultant haematologist specialising in lymphoma at the Freeman Hospital in Newcastle, said: ‘Bispecific antibodies use the patient’s own white blood cells to attack and kill the lymphoma, a form of blood cancer. The antibody has two arms: one arm attaches to the cancer cell and the other to the patient’s own white blood cell, a T-cell.
‘By bringing these cells together, the patient’s own immune system is activated and kills the cancer cell and so chemotherapy is not required. Patients don’t have the side effects of chemotherapy and often feel well on this outpatient-based treatment.‘
Glofitamab gained conditional marketing authorisation in the EU in July 2023.
Earlier in 2023, glofitamab was found to induce a fast and durable complete response rate in patients with refractory mantle cell lymphoma.
12th October 2023
NICE has recommended empagliflozin as a treatment option for some patients with chronic heart failure.
The drug (brand name Jardiance) can be considered as an option for treating symptomatic chronic heart failure with preserved or mildly reduced ejection fraction in adults, final draft guidance states.
It becomes the second NICE-recommended treatment for the condition after the approval in June of dapagliflozin, which was also approved in the EU in February.
The European Commission granted marketing authorisation for empagliflozin as a treatment for adults with symptomatic chronic heart failure in March 2022.
An estimated 150,000 people in the UK will now be eligible for treatment with empagliflozin, which should be started on the advice of a heart failure specialist, NICE said.
If a clinician considers empagliflozin to be one of a range of suitable treatments, including dapagliflozin, they should opt for the least expensive after discussing the advantages and disadvantages with the patient.
This should include taking into account the administration costs, dosage, price per dose and commercial arrangements, NICE said.
Chronic heart failure with preserved or mildly reduced ejection fraction is usually treated with standard care such as loop diuretics and treatment for other conditions the person may have, the committee said.
But given dapagliflozin is already recommended as an option, empagliflozin works in a similar way and would be offered to the same population, NICE added.
Evidence presented to the committee showed that empagliflozin plus standard care reduces the combined risk of dying from cardiovascular causes or likelihood of first hospitalisation for heart failure compared with placebo plus standard care, the guidelines said.
But there is no clinical trial evidence directly comparing empagliflozin with dapagliflozin and there were differences in how the trials were done and populations used.
‘When adjustments for these differences are made, an indirect comparison suggests the treatments have similar clinical effectiveness and a similar effect on quality of life,’ NICE said.
Other analyses also suggest the two drugs are associated with similar costs with list prices the same for both at £477.30.
In the first round of draft guidance empagliflozin had not been approved because of uncertainties over cost-effectiveness.
A version of this article was originally published by our sister publication Pulse.
27th February 2023
In an appraisal consultation document from NICE, rimegepant is not being recommended within its marketing authorisation, for the acute treatment of migraine with or without aura in adults, or for the prevention of episodic migraine in adults, who experience at least 4 attacks per month.
Rimegepant belongs to a class of drugs referred to as ‘gepants’ which are calcitonin gene-related peptide receptor antagonists. Calcitonin gene-related peptide has been associated with sensitisation and pain generation but also plays a role in vasodilatation. In a recent phase 2/3 trial, oral rimegepant, when taken every other day, was found to be effective as a preventive treatment of migraine, with its tolerability similar to placebo.
It is proposed by the manufacturer that rimegepant is used for acute migraine treatment in patients who have failed to respond to two or more triptans. However, in its consultation document, while accepting that the drug is likely to reduce pain at 2 hours post-dose more than placebo, NICE added that the evidence submitted by the manufacturer, for patients who have not responded to two triptans, is uncertain and hence requires more evidence.
Moreover, while it also reduces monthly migraine days, NICE argued that there is an absence of comparative long-term evidence to support this view. As a result, the organisation believes that this clinical uncertainty affects the certainty of the cost-effectiveness estimate and which is likely to be above what NICE considers to be an acceptable use of NHS resources.
In response to the consultation, the Migraine trust has expressed concern, stating that ‘a significant proportion of those seeking help from The Migraine Trust have an inadequate response, or contraindication to the best current acute treatment triptans, or have medication overuse headache as a result of inadequate care and treatment of their migraine.’
The statement added that ‘we believe that Rimegepant is an important opportunity to help those who have medication overuse headache and prevent others from developing it.’ These concern arose following a 2019 survey of 1,800 migraine sufferers undertaken by the trust, which found that migraine treatments caused medication overuse headache in a third of respondents.
Chief executive of the migraine trust, Rob Music said that ‘we are very disappointed by this decision and urge those affected by migraine, and particularly those without an effective treatment for migraine and who have experienced medication overuse headache, to respond to NICE’s consultation and let it know how much this new treatment option [rimegepant] is needed.’
1st February 2023
Yescarta (axicabtagene ciloleucel) is a CAR-T cell therapy that has been approved by for use by NICE in adult patients with relapsed or refractory diffuse large-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) who have already received two or more lines of systemic treatment.
Chimeric antigen receptor T-cell (CAR-T) therapy is a form of personalised immunotherapy that utilises the patient’s own immune which are modified and designed to destroy cancer cells. DLBCL is a non-Hodgkin lymphoma (NHL) and while in the UK alone, there are around 14,200 annual cases of the NHL DLBCL accounts for around 40% of all NHL cases or roughly 5,500 patients. In contrast, PMBCL is much rarer, accounting for 2 to 4 % of all NHL cases (around 330 cases in the UK).
Following initial chemotherapy, up to 45% of those with DLBCL require a second-line treatment such as a stem cell transplant and of these, around 50% ultimately relapse. Moreover, it has been estimated that only 60% of patients will survive for longer than 5 years after their diagnosis.
The decision to approve yescarta was based information from the cancer drugs fund, which showed that a total of 318 patients received treatment and showed a median overall survival of those given axicabtagene ciloleucel was 28.5 months and 45% of people were alive after three years.
The full guidance issued by NICE is expected to the published at the end of February 2023.
5th October 2021
Urothelial carcinoma is the most common form of bladder cancer, accounting for more than 90% of all bladder cancers in the UK. The main symptom is haematuria in around 80% of cases although other symptoms include increased frequency of urination, pain or a burning sensation when passing urine and weight loss. According to Cancer Research UK, between 2016 and 2018, there were approximately 10,300 new cases of bladder cancer in the UK every year.
Atezolizumab is licensed as mono-therapy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma, either after prior platinum-containing chemotherapy, or in patients who are cisplatin ineligible and whose tumours have a PD-L1 expression ≥ 5%. The checkpoint protein, programmed death-ligand 1 (PD-L1) which is present on the surface of tumour cells, normally binds to programmed death-1 (PD-1) on the surface of T-cells and prevents the T-cells from killing the tumour cells. Atezolizumab is a checkpoint inhibitor that prevents the binding of PD-L1 to PD-1 and thus restores tumour T-cell activity.
Clinical efficacy
Patients with advanced and metastatic urothelial carcinoma have a poor prognosis with 5-year survival rates as low as 6%. The standard treatment is cisplatin-based chemotherapy however, in a 2017 study 119 previously untreated patients who were cisplatin ineligible, were given atezolizumab at a dose of 1200 mg every 3 weeks until progression. The primary outcome was an objective response and which occurred in 23% of patients and a complete response was seen in 9%. The approval by NICE was based on more data, which came from IMvigor130, a multi-centre, Phase III trial, in which 1213 patients were randomised to either atezolizumab plus platinum-based chemotherapy, atezolizumab mono-therapy or placebo plus platinum-based chemotherapy. In its appraisal, NICE only considered a subgroup of 93 people, with untreated PD-L1-positive (tumour expression of 5% or more) locally advanced or metastatic urothelial cancer and who were ineligible to be treated with cisplatin.
The median overall survival was 18.6 months for atezolizumab and 10.0 months for platinum-based chemotherapy. The stratified hazard ratio was 0.50 (95% CI 0.29 to 0.87, p=0.0125), indicating that treatment with atezolizumab was associated with a significant improvement in overall survival compared with platinum-based chemotherapy. Moreover, the median progression-free survival for atezolizumab was 6.4 months compared with 6.0 months for platinum-based chemotherapy.
In its final appraisal document, NICE stated that “atezolizumab meets NICE’s criteria to be considered a life-extending treatment at the end of life. The cost-effectiveness estimates are likely to be within what NICE considers an acceptable use of NHS resources. So atezolizumab is recommended.“
Source. NICE 2021
17th September 2021
Hereditary angioedema (HAE) is a rare, inherited disorder that presents with unpredictable, recurrent attacks of oedema, leading to a rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. The condition affects around 1 in 50,000 of the population in the UK, which equates to around 1,500 people and the condition often first presents between the ages of 5 and 11 years.
The underlying cause of HAE is a mutation of the SERPING1 gene which codes for a protein, C1 esterase inhibitor (CI IHB), which regulates inflammatory pathways. This mutation can result in either low levels of C1 IHB, which is the most common presentation (type 1), accounting for around 85% of cases, or normal levels of C1 IHB, but with a reduced function (type 2). There is also a third, much rarer type characterised by normal C1 IHB levels but other mutations which also give rise to elevated levels of bradykinin. Irrespective of the underlying cause, reduced functioning of C1 IHB leads to an increased production of the vasoactive peptide, bradykinin which mediates vasodilation in subcutaneous or submucosal tissues.
The aim of treatment is to either reverse or prevent attacks with a view to improving patient’s quality of life. Treatments have been based on prophylactic use of C1 IHB concentrates, some of which have been developed as injectables for self-administration. In contrast, berotralstat, is an oral, once daily inhibitor of plasma kallikrein which is hydrolysed to release bradykinin.
NICE Approval
The NICE approval was based on the findings of the randomised phase 3 trial, APex-2, a double-blind, parallel-group study in which patients were randomised 1:1:1, to receive once-daily berotralstat in a dose of 110 mg, 150 mg or placebo. In APex-2, the primary efficacy end point was defined as the rate of investigator-confirmed HAE attacks during the 24-week treatment period. The study found that use of berotralstat led to a significant reduction in attack rate at both 110 mg (1.65 attacks per month, p = .024) and 150 mg (1.31 attacks per month, p < .001) relative to placebo (2.35 attacks per month). An extension of APex-2 was published in June 2021 in which patients originally assigned to placebo were randomised to either 110 mg or 150 mg of berotralstat and followed for 48 weeks. At the study end, mean attack rates for the 150mg group declined from a baseline of 3.06 attacks/month to 1.06 at week 48. Similarly, for the 110mg group, attack rates reduced from a baseline of 2.97 to 1.35 at week 48.
NICE has declared berotralstat is an innovative prophylactic treatment for recurrent attacks of hereditary angioedema and recommended that the drug can be used under the following circumstances.
In people 12 years and older, only if:
• they have at least 2 attacks per month and
• it is stopped if the number of attacks per month does not reduce by at
least 50% after 3 months.
Source: NICE. Berotralstat for preventing recurrent attacks of
hereditary angioedema, September 2021.
23rd July 2021
Cholangiocarcinoma (CCA) or bile duct cancer, is a rare cancer with an approximate incidence of 3.58 cases per 100,000, occurs in the tubes carrying bile into the digestive system. It can be further subdivided into two forms, depending on whether it develops within the liver (intrahepatic, iCCA) or extrahepatic (eCCA). According to Cancer Research UK, there are an estimated 1900 cases of iCCA each year but far fewer (530) cases of eCCA. Unfortunately, CCA is often asymptomatic in the early stages of the disease and consequently, it has been estimated that around 70% of patients are diagnosed at late stages due to this lack of symptoms. Figures for 2012 indicate that the 5-year survival is in both sexes is only around 5%, and in 2017, there were a total of 2523 deaths in England alone. Since a large proportion of patients are diagnosed at a late stage of the disease, surgical resection (which is perceived as the only curative treatment), is no longer an option.
Studies have shown that two-thirds of patients with cholangiocarcinoma have genomic alterations. One such alteration is in the fibroblast growth factor receptor (FGFR) pathway which is responsible for cellular migration, proliferation, survival and differentiation. There are at least four different isoforms of FGFR and genetic aberrations such as chromosomal translocations or fusions in the FGFR pathway, contribute to malignant transformation and have been observed to occur in 13% of iCCA.
Treatment
There are currently no standard care treatments for cholangiocarcinoma and no recognised therapy for patients with FGFR fusion/mutations. Pemigatinib is a potent oral inhibitor of FGFR isoforms and has been shown to be of benefit in patients with cholangiocarcinoma with FGFR alterations. Results from the FIGHT-202 study, in which previously treated patients with advanced metastatic cholangiocarcinoma with FGFR mutations, were given pemigatinib monotherapy at a starting oral dose of 13.5mg daily for a 21-day cycle (two weeks on, 1 week off). Treatment with pemigatinib for a median duration of 8 months in 108 patients, led to an overall treatment response rate of 35.5% which included three complete remission and 35 partial responders. Overall, 71 patients died, mostly because of disease progression although there were no deaths deemed to be treatment-related, leading the authors to conclude that their data supported the therapeutic potential of pemigatinib in previously treated patients with FGFR fusions.
The drug is already approved in Japan, Europe and the US and according to Helen Morement, founder of The Cholangiocarcinoma Charity, ‘the availability of pemigatinib marks a major milestone in the fight against cholangiocarcinoma, bring new hope for our patients with the devastating type of liver cancer”. The decision by NICE will not only give patients an alternative to chemotherapy but also access to molecular testing.
Source. NICE 2021
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