New treatments for people with cystic fibrosis and gating mutations
UMC Utrecht will compare repair of CFTR function by dirocaftor, a CFTR potentiator from FAIR Therapeutics with the current market-approved potentiator ivacaftor in patient-derived cells. FAIR Therapeutics is a recently established, clinical-stage Dutch biotech company that aims to develop affordable treatment for all people with cystic fibrosis through a personalized medicine approach.
The market-approved CFTR is a monotreatment for a small fraction of people with CF (PwCF) and a component of a highly effective combination treatment for the majority of PwCF. Ivacaftor also potentiates the normal, wild-type CFTR channel and could be a potential co-treatment for new genetic therapies in development. Ivacaftor is a highly expensive treatment of more than 200.000 euro per year per patient and a competitor product such as dirocaftor could be important to develop more cost-effective treatments in the future in the context of CF disease.
To compare functional rescue of ivacaftor and dirocaftor, intestinal cells from patients are used to study rescue of CFTR function by measurement of intestinal fluid transport. Fluid secretion assays in patient-derived intestinal cells correlate with in vivo therapeutic benefit, and allow testing of CFTR therapeutics such as CFTR potentiators in an individual or population-dependent manner.
Our results demonstrate comparable efficacy of ivacaftor and dirocaftor in patient-derived intestinal epithelial cells. This supports the further clinical development of dirocaftor as a cost-effective alternative for ivacaftor in the context of cystic fibrosis treatments .
