HIT-CF news: Promising results of the CHOICES CFTR modulator trial !

They are finally here: the HIT-CF team shares promising results of the CHOICES CFTR modulator trial and they suggest a good match between organoid testing and clinical outcomes! 

This text is a community adaption of the original press release of October 20, 2025. 

In October, the HIT-CF team has presented the final results of its major research project on new CFTR modulator medicines to the European Commission, which funded the study through the Horizon 2020 program. 

Over the past years, the HIT-CF project tested a new triple CFTR modulator combination, Dirocaftor, Posenacaftor, and Nesolicaftor, owned by Fair Therapeutics. The team first tested how well these medicines worked in organoids (tiny personalized models grown from patient cells) from more than 500 people with CF across 16 European countries. They did this using the FIS (forskolin induced swelling) test, a lab method that measures how well the CFTR protein works. 

The next step was a placebo-controlled, double-blind, cross-over clinical study. This means that participants receive both the real treatment and the inactive dummy treatment at different times during the study, and neither they nor the researchers know which one they are getting at any given moment.  People with CF with very diverse CFTR variants, including very rare ones, took part. The results showed a wide range of changes in lung function (from -12% to +22% predicted FEV1), along with matching improvements in sweat chloride levels and patient-reported symptoms (CFQ-R). Importantly, the improvements in the lab (the organoid tests) closely matched what happened in the clinic. 

These findings strongly support earlier statements from the European Medicines Agency that the FIS test is a reliable and meaningful way of measuring how well the CFTR protein works, and how this changes in response to possible treatments. This means FIS can help: 

1. Pre-select people for clinical trials, and 
2. Identify or predict who is likely to respond to certain modulators, based on the organoid results. This is especially precious for people with rare CFTR variants who are usually not included in commercial clinical trials. 

The study also shows that the new modulator combination from Fair Therapeutics may be a promising first-line treatment for people who show responsiveness in the FIS test, with a favorable safety profile. 

The European Commission has expressed strong support for further developing CF treatments that follow a precision medicine approach (methods that can match the right therapy to the right person based on their biology), as well as for advancing this new modulator combination so more people with CF worldwide may benefit. 

Professor Dr. Kors van der Ent, coordinator of HIT-CF, said:
“We are thrilled about these results. Despite the challenges of the pandemic and changes in industry partners, the European CF community worked with remarkable dedication to push new treatments forward.” 

Anne van Loon, CEO of Fair Therapeutics, stated:
“Around 45,000 people with CF still have no access to a potentially life-changing treatment. We are determined to keep moving forward and bring this new combination closer to the patients who need it. To do so, we are currently working hard to secure new funding in order to advance clinical testing of our triple combination.” 

Hilde De Keyser, CEO of CF Europe, added:
“The patient community has been actively involved throughout HIT-CF. We strongly support the goal of bringing treatments to people with ultra-rare variants and to those living in underserved regions.” 

The HIT-CF Consortium is made up of partners from across Europe, including university hospitals, research institutes, patient organisations, and industry partners. The consortium wants to thank the people with CF from all over Europe who took part in this project, for their patience and dedication – this wouldn’t have been possible without them!   

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