New paper published on the future of cystic fibrosis therapies

A changing landscape 

There’s no doubt that the landscape for people with CF has changed dramatically in recent years. The introduction of CFTR modulator medicines like Kaftrio means that many people are living longer and healthier lives. But for those people with CF who cannot benefit from or tolerate CFTR modulators, the future can still feel very uncertain. For this group of people, alternative therapies are desperately needed. 

We know that this is a priority for everyone in the CF community, as reflected in the recent refresh of your CF research priorities – “What options are available for those not able to take current CFTR modulators (including rarer mutations, not eligible and unable to tolerate)?“ was identified as the top research priority in November 2022. 

This review highlights some of the approaches underway, including: potential medicines for people with specific group of CF mutations known as ‘Class 1’ mutations (Class 1 mutations are also known as ‘stop’ or ‘nonsense’ mutations); ways to test the effectiveness of CFTR modulators for very rare mutations, where these medicines haven’t been tested; and medicines that have the potential to benefit everyone with CF whatever CF mutations they have.  

One example of a type of medicine that may benefit everyone with CF is genetic therapies. Recently we announced a new funding partnership with the US-based CF charity Emily’s Entourage to develop novel ways to deliver a genetic therapy for CF in the lab. If successful, this research could lead to a treatment for everyone with CF in the future.  

You can read more about the research we’re funding to tackle the underlying cause of CF, including genetic therapies here.  

Current challenges in CF care 

Advances in our understanding of CF mean that there are more effective treatments available, so people with CF are living longer than ever. However, getting older with CF can bring its own health challenges and we know that this is a concern for many people, as you identified ‘How do we manage an ageing population’ in the CF community’s top 10 CF research priorities. The review looks in detail at some of the current and future challenges in CF care, including age-related symptoms and complications.  

Although respiratory and gastrointestinal symptoms may continue to remain an important part of CF care, new and emerging complications associated with growing older means the CF care community must continually adapt and respond to the needs of a changing population. For example, this may include long term effects of living with CF diabetes and the effects of age-related bone loss.  

At the Trust, we have already played an active role in bringing together a wide range of researchers to look into why people with CF may be increased risk of developing cancer and how to prevent it, as research has shown that CF is linked to an increased risk of bowel (or colorectal) cancer, which is mentioned in the review In January 2021 we began funding a Strategic Research Centre (SRC) award led by Professor Stephen Renshaw. More information on cancer and CF is available on the Trust’s website 

You can read more about the research we’re funding to better understand and treat the symptoms of CF here.  

Designing new treatments for the future 

For many people with CF there is still a need for improved treatments, and the CF research and care community are fully committed to delivering them. All new treatments need to be tested in clinical trials. The review explains some of the new challenges in designing and running clinical trials in CF, such as the need to identify and recruit individuals with rarer gene mutations, and importantly highlights steps that are underway to address them. The Trust’s Trials Accelerator programme and our UK CF Registry will contribute to making progress in this area. 

Because there are fewer people with CF unable to benefit from CFTR modulators, changes to how clinical trials carried out will need to be made, to test new medicines designed specifically for this group. These include applying new statistical methods of ensuring that the beneficial effects of new treatments are real and developing new ways to recruit people into these studies, for example making it easier for people to take part in clinical trials nearer to their homes. The CF project as part of the NIHR BioResource for Rare Diseases will also help identify suitable participants for future clinical trials. Find out more about the project and how you can get involved on the CF BioResource page of our website. 

The overall improved health for people with CF on CFTR modulators means that some changes are needed to how clinical trials are conducted, this includes how to compare the benefits that a new medicine may provide above ‘standard’ treatment, and more sensitive tests in the clinic to detect any benefits. For example, this may be the use of lung clearance index in the place of FEV1 as a way to assess the effects of a new medicine on lung function. 

Tackling CF around the world 

Inequity in access to care is also a challenge which is important we continue to address. Even in the UK, in what many of us would consider a well-resourced healthcare system, there have been long periods of negotiation over new and high-cost drugs which in some cases have led to delays in access.  

There is also increasing evidence to show that CF is not the rarity it was previously considered in countries with non-white populations. Rare CFTR mutations are more common in these populations, which means a major unmet need in access to CFTR modulator medicines.  

Alongside research to develop treatments for those with rare mutations, the Trust is looking at how we can increase diversity in clinical trial participation in our Trials Accelerator programme, including addressing any barriers to accessing trials that people within the CF community may face. 

Another example is the European Cystic Fibrosis Society’s (ECFS) twinning project, which joins up highly experienced centres with those in less well-resourced areas for the sharing of clinical expertise, protocols and training materials.  

Here at the Trust, we won't stop until everyone with CF in the UK can access the care, support and treatments they need.  

Dr Lucy Allen is Director of Research and Healthcare Data at the Trust and one of the authors of this review. She commented:  

You can read the full Nature Communications review paper here.  

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