Continuing the search for treatments for everyone with CF
CFTR modulators have transformed life for many people with CF. But they don't work for everyone. Some people with CF have gene variants that modulators can’t help, and others cannot tolerate them. Even for those who do benefit, modulators manage CF rather than cure it. That's why finding new treatments that work for everyone with cystic fibrosis is vital and remains one of our top research priorities.
There are several different approaches being explored. Genetic therapies are among the most exciting. These work by correcting or adding to the genetic material in lung cells to help them make a working CF protein. This protein can either work on its own or alongside modulators.
Researchers are also looking at other approaches such as alternative channel therapies, which aim to restore the movement of salt and water across the airway without targeting the CF protein at all.
The Trust is also funding research to prevent, understand and treat other symptoms of CF outside of the lung. These include lab studies to develop new ways to treat CF diabetes, and studies to understand more about the range of gut symptoms people with CF experience, so these can be more specifically treated in the future.
Recent setbacks in genetic therapy trials
In recent months, two early-phase CF genetic therapy trials have been stopped earlier than planned. Boehringer Ingelheim made the decision to stop the Lenticlair gene therapy study, and more recently Vertex stopped their VX-522 mRNA therapy trial.
We know this may be frustrating news and we share that disappointment. A huge thank you to everyone who took part in these studies, to their families, and to the clinical teams who supported them. What they did matters, even when the outcome is not what we hoped for.
But, it is important to remember that all clinical trials are research studies. They are run because we don't know what the results will be. Early phase trials in particular, are designed to test whether a treatment is safe and well tolerated. A treatment’s effectiveness, or how well it works, is tested later, in bigger studies. When a trial stops early, it is always disappointing. But no research is wasted. Scientists and clinicians learn from every study, even those that are stopped early. Those lessons help shape the better design of therapies and trials in the future.
Although this is a setback, it's the kind of thing that happens in most drug development programmes. In CF there are some particular challenges that make developing new treatments even harder, so this is likely to be a long journey with more bumps along the road.
Professor Alex Horsley, Director of Manchester Adults CF Centre, Director of the Pulse-CF Innovation Hub and member of CTAP’s Research Scientific and Oversight Board (RSOB)
“But the good news is that companies, charities like Cystic Fibrosis Trust and the US CF Foundation, and the wider research and clinical communities, all remain committed to helping us achieve the goal of effective treatments for everyone with CF. These therapies have the potential to help many conditions beyond CF, giving companies even stronger reasons to keep going.
Genetic therapy research is still moving forward
The stopping of two trials does not mean that genetic therapy research for CF is stopping. Several other companies have early-phase trials underway or in the process of being set up. These are being discussed with and supported by the UK CF Clinical Trials Accelerator Platform (CTAP).
Alongside these clinical trials, lab-based researchers around the world are working to understand how future genetic therapies could work, and how to get them to the right cells in the lung. For example, researchers from across Europe within the Trust-funded Karen Menzies PTSuppress Strategic Research Centre programme are designing chemicals in the lab that could be used as CF medicines in the future, for those with a specific type of ‘Class 1’ CF variants.
Understanding how to deliver genetic therapies effectively to the right cells in the lung is crucial and is one of the hardest parts to get right. This is an area of research that the Trust has invested in for many years. Read about two recent studies in this area in our research impact report.
What the Trust is doing
We're working hard to find and support new opportunities which will help address the priorities of the CF community, identified in the JLA PSP priority refresh project. For example, CTAP has recently established a Commercial Studies group whose role is to help us seek out companies working in areas that could benefit people with CF, including in genetic therapies, and to build those relationships. Our CF Accelerate programme is designed to make it easier for companies to run CF clinical studies in the UK. We also continue to fund high quality research to develop effective treatments for all.
Looking ahead
Later this week we're attending the European CF Society Conference - the biggest CF research conference in Europe. We’ll be there to listen, connect with researchers and to look for new opportunities to support the right research.
We know that the path to finding new treatments is not straightforward. But we remain committed to finding treatments that will mean that everyone with CF can live a life without limits.