MECHELEN, Belgium—Galapagos NV has announced the first dosing in its Phase 2 exploratory program of GLPG1837 in patients with cystic fibrosis (CF). GLPG1837 is a candidate CFTR potentiator drug in clinical development for the treatment of Class III mutations in cystic fibrosis. The SAPHIRA Phase 2 program will explore the safety, tolerability and efficacy properties of GLP1837 in CF patients with a G551D (SAPHIRA 1) or S1251N (SAPHIRA 2) Class III mutation. Topline results from the SAPHIRA Phase 2 program are expected in Q4 2016.
"Today's announcement is a landmark achievement in our CF program, with the first CF patient being treated with a Galapagos potentiator," said Onno van de Stolpe, CEO of Galapagos. "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."
Details of the SAPHIRA Phase 2 program: SAPHIRA 2, an open-label study of two doses of GLPG1837 in at least six CF patients with the S1251N mutation, was first dosed in a patient last week. SAPHIRA 1, an open-label study of three doses of GLPG1837 in at least 12 patients with the G551D mutation, is expected to begin dosing soon. The SAPHIRA Phase 2 program will explore the safety, tolerability, efficacy, and medicine-like properties of GLPG1837 in patients in six EU countries and Australia. Primary objectives are to evaluate the safety and tolerability; secondary objectives are to assess changes in sweat chloride from baseline as the biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function and to explore the changes in pulmonary function (forced expiratory volume in 1 second (FEV1) from baseline. Both studies will include subjects treated with Kalydeco1 as well as those who are naive to this drug. In each study, different doses of GLPG1837 tablets will be administered twice daily for a total duration of four weeks.
In September 2013 Galapagos and AbbVie, a global biopharmaceutical company, entered into a global collaboration agreement focused on the discovery and worldwide development and commercialization of potentiator and corrector molecules in a potential triple combination therapy for the treatment of CF. Under the terms of the agreement, AbbVie made an upfront payment of $45 million to Galapagos. Upon successful completion by Galapagos of clinical development through to completion of Phase 2, AbbVie will be responsible for Phase 3, with financial contribution by Galapagos. Galapagos has earned $20 million in milestone payments to date and is eligible to receive up to $340 million in total additional payments for developmental and regulatory milestones, sales milestones upon the achievement of minimum annual net sales thresholds and additional tiered royalty payments on net sales, ranging from mid-teens to 20 percent.
CF is a rare, life-threatening, genetic disease that affects approximately 80,000 patients worldwide and approximately 30,000 patients in the United States. CF is a chronic disease that affects the lungs and digestive system. CF patients, with significantly impaired quality of life, have an average lifespan approximately 50 percent shorter than the population average, with the median age of death at 40. There currently is no cure for CF. CF patients require lifelong treatment with multiple daily medications, frequent hospitalizations and ultimately lung transplant, which is life-extending but not curative. CF is caused by a mutation in the gene for the CFTR protein, which results in abnormal transport of chloride across cell membranes. Transport of chloride is required for effective hydration of epithelial surfaces in many organs of the body. Normal CFTR channel moves chloride ions to outside of the cell. Mutant CFTR channel does not move chloride ions, causing sticky mucous to build up on the outside of the cell. CFTR dysfunction results in dehydration of dependent epithelial surfaces, leading to damage of the affected tissues and subsequent disease, such as lung disease, malabsorption in the intestinal tract and pancreatic insufficiency.
Galapagos is a clinical-stage biotechnology company specialized in the discovery and development of small molecule medicines with novel modes of action. The company’s pipeline comprises three Phase 2, two Phase 1, four pre-clinical, and 20 discovery studies in cystic fibrosis, inflammation, fibrosis, osteoarthritis and other indications. Galapagos has discovered and developed filgotinib. The goal, in collaboration with Gilead, is to bring this JAK1-selective inhibitor for inflammatory indications to patients all over the world. Galapagos is focused on the development and commercialization of novel medicines that will improve people's lives. The Galapagos group, including fee-for-service subsidiary Fidelta, has approximately 400 employees, operating from its Mechelen, Belgium headquarters and facilities in The Netherlands, France, and Croatia.