Adding GLPG2737, Galapagos’ investigational CFTR corrector, to Vertex’s Orkambi (lumacaftor/ivacaftor) enhances the effectiveness of the treatment in cystic fibrosis patients with two copies of the F508del mutation, topline results from a Phase 2 trial show.
Conducted at multiple sites in Germany, the Phase 2 PELICAN clinical trial (NCT03474042) evaluated the effectiveness, safety, and tolerability of the combo therapy in 22 adults with two copies of the F508del mutation in the CFTR gene who were receiving stable treatment with approved therapy Orkambi.
“The PELICAN trial is the first to evaluate GLPG2737 as a C2 corrector in CF patients on top of Orkambi and showed CFTR on-target activity with GLPG2737 in combination with Orkambi,” Piet Wigerinck, MD, chief scientific officer of Galapagos, said in a press release.
Participants were randomized to receive oral capsules of GLPG2737 or a placebo with Orkambi twice daily for 28 days.
Analysis of the participants’ lung function, evaluated by absolute change from baseline — the starting point of the trial — in percent predicted forced expiratory volume in one second (ppFEV1), revealed a positive effect of the combo therapy. Patients who received GLPG2737 experienced an improvement of 3.4% by day 28 compared with those treated with a placebo.
GLPG2737 also significantly reduced sweat chloride levels, which are often increased in CF patients due to impaired CFTR activity. The researchers reported a significant decrease in mean change of 19.6 mmol/L from baseline in the GLPG2737-treated group compared with placebo.
In general, the combo therapy was well-tolerated, with adverse events mild to moderate in severity. The incidence of adverse events was similar in both treatment groups, and no treatment-related serious adverse effects were reported. There were no deaths or premature discontinuations due to adverse events during the study period.
More details on the effects of the combo treatment will be disclosed at a future conference, according to Galapagos.
A potentatior in CF works by keeping the CFTR gate open to help chloride flow through it; correctors help the CFTR protein obtain the proper 3D shape to allow it to move to the cell’s surface where it works as a gate for chloride ions.
“We have initiated dosing in the FALCON trial, in which we aim to evaluate higher exposures of GLPG2737 in CF patients and further understand the potential synergistic effect of GLPG2737 on top of our own dual combination compounds,” Wigerinck said.
The open-label FALCON trial is currently recruiting adults with confirmed CF who have two copies of the F508del mutation or one copy of this genetic mutation plus a potentiator nonresponsive mutation. The study is expected to enroll about 24 participants across several sites in Europe.
Initial results of this trial are expected to be announced in the third quarter of 2018.
In the meantime, Galapagos’ partner, AbbVie, has decided not to continue evaluating the triple combination of GLPG2222 and GLPG2737 with the potentiator GLPG3067. The company is currently reviewing the future of its CF collaboration with AbbVie.