10 June 2025
As part of Cystic Fibrosis (CF) Awareness Week, we sat down with Professor Nicholas Simmonds to discuss the advances made in CF care thanks to research.
Professor Simmonds is the associate director and consultant physician of the Adult CF Centre at Royal Brompton and Harefield hospitals. He is a specialist in the care and management of adults living with CF and leads one of the UK’s most advanced services for diagnosing complex or uncertain cases of CF.
In addition to his clinical work, Professor Simmonds is also a leading figure in CF clinical trials, helping to shape how new treatments are tested and brought to patients, and leading on global, multi-centre trials.
Over the past 10 years, the treatment and management of CF has undergone a remarkable transformation, driven by advances in precision medicine, access to breakthrough therapies, and improved care models - all thanks to research.
Professor Simmonds shed some light on these research breakthroughs and his thoughts on the future of CF care.
Q: There have a been a lot of changes in the world of CF, with new treatments and therapies becoming available. Can you tell us a little about how CFTR modulators in particular have changed the treatment landscape for CF?
It’s been a truly exciting time for those patients who are eligible for CFTR modulators, these new treatments have been really transformative on so many levels.
The biggest change has been in relation to lung function and infection frequency, with patients developing fewer infections, needing fewer antibiotics, and requiring fewer visits to the hospital.
This journey has been going on for over 12 years now, but the pipeline is strong and continues with a new triple therapy which will hopefully become available in the UK soon. This new therapy has been through drug trials at several centres, including here at Royal Brompton Hospital, and hopefully we’ll be able to extend the benefits to even more people with CF.
Q: What are some other key new therapies that are being trialled at the moment?
The other area I've been particularly involved with, which I think is truly exciting and novel, is trying to find therapies for people with rare CF mutations. These are the mutations where they generally do not respond to modulators, or where we don't really know if they respond.
Since 2018, Royal Brompton Hospital has been a lead site for a trial called HIT-CF which is a fantastic example of personalised medicine. It involved taking a small biopsy from an individual with CF who has rare genetic mutations, and sending it to our expert collaborators in Utrecht, Netherlands.
They used the biopsy to grow mini organs, called organoids, which contain the individual's genetics relating to CF. We then used these organoids to test different types of medications to see if they respond to different forms of modulators.
We’re currently undertaking the second stage of the trial, called CHOICES, where we've taken those individuals, whose organoids responded, to determine whether the responsiveness we saw in the labs can also be seen in the individual by looking at changes in their lung function, infection frequency etc.
The aim is to be able to look at the individual genetics of a person with CF and be able to say, “this person will respond to this type of drug so let’s give them that”.
We’re now coming to the end of the trial, which is very exciting and hopefully we'll have results in the coming months.
Q: You mentioned genetic therapies - what’s the current outlook on that for CF?
Based on what we know and the current science, modulators will definitely not be suitable for every single person with CF, and about 5-10% of people with CF will need some form of gene therapy instead rather than a modulator therapy.
Some people with CF have a type of mutation where the CF protein is not produced at all so the modulators are never going to work for them because they require the protein to work on. These people need gene therapy where you correct the fault in the DNA, or RNA therapy where you correct or replace the faulty RNA.
So, gene therapy and RNA therapy are the next really important phases of drug development for CF.
Researchers at Imperial College and Royal Brompton, led by Professor Eric Alton, have been leading in gene therapy for CF for a very long time, as part of the UK CF Gene Therapy Consortium. The group are currently running a gene therapy trial which involves a type of virus (lentivirus) being used to deliver the “correct” gene directly into the lungs through a nebulised treatment.
Internationally, there are other gene therapy and RNA therapy trials ongoing, and these trials are really important so that we that we ensure we can treat everyone.
Q: Are there any other novel approaches in the pipeline for treating or managing CF that excite you?
Absolutely. We’re currently involved in an early phase clinical trial which is treating CF in a different way to what I've just described. This trial aims to treat the underlying sodium channel fault.
In CF the sodium channel is faulty and is responsible for taking in too much salt and water into the cells which is why you get thick, sticky mucus. If you can correct or modify how that sodium channel works, theoretically you should see clinical benefits.
This trial aims to specifically treat the epithelial sodium channel (‘ENaC’) through nebulised therapy into the lungs.
This is an exciting trial to be part of because this is an area where there have been trials in the past using different products which haven’t quite worked, but the early phase results from this trial have been promising..
Q: We’ve talked a lot about the treatments, and potential treatments in the pipeline, but what about how CF is diagnosed? What are some of the advancements that have been made in that area?
A particular area of interest of mine is in difficult diagnosis. It might seem like CF is an obvious, straightforward condition to diagnose, and it is for the majority of patients, but for an important minority, it really isn't.
Diagnosing some people with CF can be very complicated because the traditional tests, such as the sweat test, or genetic tests, don’t always give us the full answer, and that's because the genetic fault in CF can be very complicated.
I was lucky enough to be awarded funding by the CF Trust to set up a research programme to improve our ability to diagnose people with rare mutations.
The programme will be undertaken with our collaborators in Utrecht again, along with Kings College London, where we will take biopsies from people with rare mutations or are difficult to diagnose, and again, culture organoid products, which I mentioned previously.
The plan is to see if the organoids respond as expected in someone with CF and compare this to other more traditional forms of CF testing.
This is incredibly important from a patient perspective because we’re aiming to provide a conclusive diagnosis and making sure this group don’t miss out on opportunities for effective novel treatment currently available.
Q: And finally, what do you foresee being the main focus of research for CF over the coming years?
Beyond the work I’ve already mentioned there is still a whole host of really important clinical research that needs to be done.
The gains we’re seeing from these novel therapies that treat the underlying basic defect in CF are of course, fantastic but we want to make sure to manage and treat some of the new complications that are developing as a result of individuals living longer.
One area that's discussed a lot, is the issue of extrapulmonary complications which are complications that happen outside the lungs. This includes some of the complications that arise from CF diabetes and is of particular importance because as individuals with CF continue to live longer, we're going to see even more diabetes.
Unfortunately, cancer is another area that is of increasing concern in CF, particularly bowel cancer. For a long time now we've known there to be an association between CF and bowel cancer, but we don't fully understand why. Again, with improvements in survival, we have to make sure we're screening appropriately and have the right tools to do it.
Cardiometabolic risk is an area of research which is rapidly developing. We're seeing people with CF who are developing cardiometabolic problems at a relatively young age, and we need to understand why and how best to treat it.
I also wish to highlight that its important to develop non-drug related interventions because CF is a multi-system disease. With my physiotherapy colleague, Dr Gemma Stanford, we are leading a large multi-centre randomised controlled trial of a CF-specific yoga intervention, called YOGA-CF; it is progressing well with over 300 patients recruited!
Increasingly, more women with CF are having babies, which is a fantastic success story but brings with it a new set of unanswered questions around reproductive, maternal and child health, including the possible effects of CFTR modulator drugs on pregnancy and in babies.
Dr Imogen Felton, respiratory consultant, has set up a strategic research centre, with funding from the CF Trust, to undertake a programme of work to try and answer these really important questions of this exciting new field.
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