CF is triggered by a mutation in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in abnormal transport of chloride across cell membranes. Such transport is crucial for effective hydration of epithelial surfaces in several organs. Normally, the CFTR channel transports chloride ions to the outside of the cell, but mutant CFTR doesn’t, leading to sticky mucous build up on cells. CFTR dysfunction damages the affected tissues and can lead to lung disease, malabsorption in the intestines, and pancreatic insufficiency due to the dehydration of dependent epithelial surfaces.
The Phase 2 open-label study will evaluate two, twice daily doses of GLPG1837 over four weeks in at least six CF patients with the S1251N mutation, and is taking place in Europe and Australia. Primary endpoints are the drug’s safety and tolerability, and secondary endpoints are its effectiveness and medicine-like properties as determined through changes in sweat chloride from baseline — a CF biomarker of CFTR ion channel function — and changes in pulmonary function (forced expiratory volume in one second [FEV1]) from baseline.
Another trial, called SAPHIRA 1, is an open-label, four-week study of three doses of GLPG1837 in at least 12 CF patients with the G551D mutation, and is expected to begin dosing soon. The two studies will include subjects who have been treated with Kalydeco (ivacaftor), a U.S. Food and Drug Administration-approved CF treatment, and those naïve to the drug.
“Today’s announcement is a landmark achievement in our CF program, with the first CF patient being treated with a Galapagos potentiator,” Onno van de Stolpe, Galapagos’ CEO, said in a press release. “Recruitment for the SAPHIRA program is rapid, and we look forward to seeing to what extent our promising in vitro data translates into clinical results. We aim to start and report a number of clinical studies with additional compounds in the CF portfolio throughout 2016.”
Galapagos is collaborating with AbbVie in this program. Under terms of their 2013 agreement, Galapagos will lead the clinical development of GLPG1837 through these Phase 2 trials. If successful, AbbVie will continue development in a future Phase 3 clinical study.