The HIT-CF Consortium presented its final results on the development of new CFTR-modulator compounds to the European Commission which funded the project under the European Union’s Horizon 2020 research and innovation program (755021).
Cystic Fibrosis is a genetic lethal disorder affecting the lungs, digestive system, and other organs. It’s caused by mutations in the CFTR gene, leading to thick, sticky mucus buildup. This clogs airways, traps bacteria, and disrupts digestion. Without CFTR modulator therapy median survival is limited to early adulthood.
The clinical effect of the CFTR-modulator combination Dirocaftor-Posenacaftor-Nesolicaftor, as licensed by Fair Therapeutics was strongly related to the ex vivo effects in people with Cystic Fibrosis (pwCF) with all types of genetic (including ultrarare) variants. In placebo-controlled double blinded studies, changes in percentages predicted FEV1 ranged from -12% up to +22% with concomitant changes in sweat chloride levels and patient related outcomes (CFQ-R). Ex vivo responses were measured with the forskolin induced organoid swelling (FIS) assay in over 500 pwCF in 16 different European Countries.
The study also shows promising clinical effects of the new CFTR-modulator combination Dirocaftor-Posenacaftor-Nesolicaftor of Fair Therapeutics as first-line treatment in pwCF who show responsiveness in the FIS assay, with a favorable safety profile.
The results strongly underline the earlier supporting statement of the European Medical Agency that the FIS assay is a reproducible in vitro biomarker with strong biological rationale and that FIS can be used to select responders in vitro and propose treatments to patients with rare mutations not assessed in clinical trials with CFTR modulators.
The European Commission strongly supports the further development of both biomarker driven prescription of disease modifying drugs in chronic diseases as well as further development of the new CFTR-modulator combination for pwCF worldwide.
Prof dr Kors van der Ent at the University Medical Center Utrecht, coordinator of the HIT-CF project said: ‘We are really thrilled about the results of our project. Despite all hurdles during the pandemic and changing commercial partners, the entire European CF community showed perseverance and dedication to realize treatments for pwCF.’
Fair Therapeutics (Fair TX) is a privately held, clinical-stage biopharmaceutical company developing personalized treatments for cystic fibrosis.
Mrs Anne van Loon, CEO of Fair Therapeutics stated: ‘FAIR Therapeutics is proud to show the results of their new modulator combination. Around 45,000 diagnosed people with CF do not have access to a life-saving treatment. We are determined to set next steps in the development of this combination and complete our mission to transform CF treatment.’
Mrs Hilde de Keyser, director of CF-Europe, the umbrella patient organization of pwCF in Europe mentioned: ‘The patient community was actively involved in the HIT-CF project and we strongly support the goal to realize treatment for patients with ultra-rare mutations and underserved areas.’
The HIT-CF Consortium consists of the University Medical Center Utrecht (coordinator), the Katholieke Universiteit Leuven, Faculdade Ciencias da Universidade de Lisboa, The European Cystic Fibrosis Society, CF-Europe, FAIR Therapeutics, HUB Organoids, Julius Clinical and Patergus.
