Galapagos Initiates Phase 1 Trial of New Therapy for CF Treatment

Galapagos initiated a Phase 1 trial to evaluate its investigational drug GLPG3067 for cystic fibrosis (CF), triggering a $7.5 million milestone payment from AbbVie, its collaboration partner.

Galapagos and AbbVie began a global collaboration in September 2013 to discover, develop and commercialize potentiator and corrector molecules for the treatment of CF.

In an effort to bring more effective therapies to CF patients, the two companies developed a portfolio of candidates addressing three complementary components for a potential combination therapy based on the CFTR gene, which is defective in CF. The CFTR gene encodes an ion channel important for the transport of chloride across cell membranes.

The goal is to develop a triple CFTR combination therapy that might address 90 percent of all CF cases. This combination therapy will include molecules that restore two of the required CFTR activities: the correctors, which will increase CFTR protein levels at the cell surface, and the potentiators, which will induce the correct opening of the CFTR channel.

Galapagos is evaluating the potentiator GLPG2451 and the corrector GLPG2222 in healthy subjects. The goal is to add corrector GLPG2737 to make a triple combination therapy, which will be first evaluated in healthy subjects and then in patients suffering from a specific mutation in the CFTR gene: the F508del mutation.

Triple combinations of CF treatments have been consistent in showing restoration of healthy activity levels in in vitro assays with human bronchial epithelial (HBE) cells of patients with this mutation.

These combinations were found to result in increased chloride transport compared to Orkambi in HBE cells with the F508del mutation – Orkambi (lumacaftor/ivacaftor) is a prescription medicine sold by Vertex for the treatment of CF in patients older than 12 who have two copies of the F508del mutation.

The aim of this Phase 1 trial is to evaluate the safety, tolerability and drug properties of oral single and multiple ascending doses of GLPG3067. The safety and tolerability of a potential combination therapy with GLPG2222 will also be assessed.

The randomized, double-blind, placebo-controlled, single center study is being conducted with 48 healthy volunteers in Belgium.

In the first part of the study, single-ascending doses of GLPG3067 will be tested. In a second part, multiple-ascending doses will be administered daily for two weeks. In the third and last part of the study, the combination therapy (GLPG3067 and GLPG2222) will be administered for two weeks.

Topline results are expected to be disclosed at a future medical conference.

“We continue to explore additional molecules to enrich our growing portfolio of cystic fibrosis drug candidates,” Piet Wigerinck, Galapagos’s chief scientific officer, said in a press release. “We plan to initiate multiple studies within our CF portfolio in the course of this year as we get closer to our goal of initiating a patient evaluation of a triple combination therapy by mid-2017.”