Galapagos Doses Healthy Subject with Combo Treatment in Phase 1 CF Study

Researchers conducting a Phase 1 study for cystic fibrosis (CF) have dosed their first healthy volunteer with a combination of the novel drugs GLPG2222 (a corrector) and GLPG2451 (a potentiator), the Belgian company Galapagos announced.

The randomized, placebo-controlled study (NCT02788721) involves at least 40 healthy participants in Belgium. It aims to evaluate single and multiple ascending oral doses of GLPG2451 as a single agent compared to placebo, and also the safety, tolerability and drug properties (pharmacokinetics) of 14 days of co-administration of combined multiple doses of GLPG2451 and GLPG2222, compared to GLPG2451 and placebo.

Galapagos and AbbVie are collaborating to design therapies for CF, aiming for a triple-combination treatment that corrects and restores the activity of the CFTR channel (corrector drugs) — which is deficient in CF patients — and allows for the channel’s proper opening (potentiator drugs).

GLPG2222 (C1) is a new CFTR corrector, designed to fix and partially restore the F508del mutation of the defective CFTR protein in CF. GLPG2451 is the second potentiator, and the third compound in the portfolio to enter the clinic.

Combined, these compounds are designed to allow chloride ion transport through CFTR channels and significantly improve hydration of the lung and pancreatic duct surface, ameliorating the symptoms of CF patients.

Triple combinations of CF drugs have been reported to restore CFTR activity levels in in vitro assays with human bronchial epithelial (HBE) cells of CF patients with the CFTR F508del mutation. In fact, the combination of GLPG2222 and a CFTR potentiator was found to restore the function of F508del CFTR, as reported in November 2016.

“We are pleased to have initiated our first dual-combo Phase 1 study with our potentiator and C1 corrector for cystic fibrosis,” Galapagos CSO Piet Wigerincks aid in a recent press release. “This step brings us closer to our goal of initiating a patient evaluation of a triple-combination therapy by mid-2017.”

Galapagos is also evaluating GLPG2222 as an add-on therapy to Kalydeco (ivacaftor) in CF patients harboring one F508del CFTR mutation and one gating mutation.

The ALBATROSS Phase 2a clinical trial (NCT03045523) is evaluating the safety and tolerability of two doses of oral GLPG2222 or a placebo in up to 35 subjects with CF for 29 days. Study participants must be on stable treatment with Kalydeco for at least 28 days before starting the trial.