Cystic fibrosis treatment is making strides with the recommendations of Ivacaftor–Tezacaftor–Elexacaftor (IVA–TEZ–ELX) plus ivacaftor (IVA) alone for patients aged 2 and over who have at least one F508del mutation in the CFTR gene. This therapy is supported within its marketing authorisation as an effective option for managing cystic fibrosis.
Similarly, Tezacaftor–ivacaftor (TEZ–IVA) plus IVA alone is recommended for individuals aged 6 and over with specific CFTR gene mutations. Additionally, Lumacaftor–ivacaftor (LUM–IVA) is advised for patients aged 1 and over who have two copies of the F508del mutation in the CFTR gene. These treatments are endorsed provided they are supplied according to the commercial arrangements made by the companies.
Cystic Fibrosis Treatments: New CFTR Modulators Offer Promising Alternatives for Improved Outcomes
Cystic fibrosis is a severe condition affecting multiple organs, primarily the lungs, digestive system, and liver, leading to a significantly reduced life expectancy and quality of life. Standard treatments for cystic fibrosis involve extensive and time-consuming daily regimens, including airway clearance, physiotherapy, and medication. Despite these efforts, many patients face frequent hospitalisations due to lung infections and other complications. The new CFTR modulators offer a promising alternative by improving lung function, growth, weight gain, and reducing lung infections more effectively than traditional therapies.
Clinical trial evidence demonstrates that IVA–TEZ–ELX provides substantial benefits, including improved lung function, growth, and weight gain, and a reduction in lung infections, which are likely to be sustained with continued treatment. TEZ–IVA and LUM–IVA also show improvements in these areas, although the extent of benefits is smaller compared to IVA–TEZ–ELX. Considering the severity of cystic fibrosis and its impact on quality and length of life, these treatments are deemed cost-effective and acceptable uses of NHS resources.
IVA–TEZ–ELX (Kaftrio, Vertex) is approved for use in combination with ivacaftor for treating cystic fibrosis in patients aged 2 years and older who have at least one F508del mutation in the CFTR gene. TEZ–IVA (Symkevi, Vertex) is indicated for treating patients aged 6 years and older who are homozygous for the F508del mutation or have a combination of F508del and another specific mutation in the CFTR gene. LUM–IVA (Orkambi, Vertex) is approved for treating cystic fibrosis in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.
IVA–TEZ–ELX and TEZ–IVA are available in various dosages in tablets or sachets. The specific dosage schedules for these treatments are outlined in their respective summaries of product characteristics (SPC). The list prices for these treatments vary: IVA–TEZ–ELX tablets and sachets cost £8,346.30 per pack; TEZ–IVA tablets are priced at £6,293.91 per pack; LUM–IVA tablets and sachets are £8,000 per pack; and IVA tablets and sachets range from £7,000 to £14,000 per pack, depending on the dosage.
Cystic Fibrosis Management Transformed by CFTR Modulators: Expert Insights
Clinical experts have emphasised that cystic fibrosis is a multi-system condition requiring intensive daily management. The high treatment burden includes airway clearance, physiotherapy, nebulised treatments, pancreatic enzymes, and frequent hospitalisations. The introduction of CFTR modulators like IVA–TEZ–ELX, TEZ–IVA, and LUM–IVA has significantly changed the management of cystic fibrosis, transforming it from a progressive, life-limiting illness to a more manageable chronic condition.
Patient testimonies highlight the transformative impact of CFTR modulators, reporting improved physical health, mental wellbeing, and quality of life. The treatments have led to better lung function, reduced coughing, fewer hospitalisations, and less time spent on intensive treatments. This has allowed patients to pursue education, employment, and family life, which were previously challenging due to the debilitating nature of cystic fibrosis.
The clinical evidence base for CFTR modulators includes numerous trials demonstrating the benefits of these treatments across different age groups and genotypes. Commonly reported outcomes include improvements in lung function, reduction in pulmonary exacerbations, and better nutritional status. The evidence shows that IVA–TEZ–ELX provides substantial benefits, while TEZ–IVA and LUM–IVA also offer improvements but to a lesser extent.
The long-term effectiveness of CFTR modulators is supported by data from the UK Cystic Fibrosis Registry (UKCFR) and other sources. The data collection agreement between NHS England, NICE, and other stakeholders aims to resolve key uncertainties by providing comprehensive real-world evidence. The findings indicate that the benefits of CFTR modulators are sustained over time, contributing to better health outcomes and quality of life for patients.
The economic model developed by the external assessment group (EAG) incorporates various factors, including health-state utility values, treatment-specific utility benefits, and disease-management costs. The model predicts that CFTR modulators offer cost-effective solutions for managing cystic fibrosis, with significant cost savings from reduced use of other prescribed medicines and healthcare resources.
The recommendations for IVA–TEZ–ELX, TEZ–IVA, and LUM–IVA reflect their clinical and economic value in treating cystic fibrosis. These treatments offer substantial benefits, transforming the management of cystic fibrosis and improving the quality of life for patients. The positive impact of CFTR modulators is evident in the clinical trial data and real-world evidence, making them a valuable addition to the NHS resources for managing this challenging condition.
Resource: National Institute for Health and Care Excellence, July 24, 2024
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