Adding investigational CFTR corrector GLPG2222 safely improved disease parameters in cystic fibrosis (CF) patients treated with Kalydeco (ivacaftor), reported the therapy’s Belgian developer, Galapagos, citing Phase 2 clinical trial data.
The benefit of adding GLPG2222 was similar to that seen in an earlier study of a tezacaftor-Kalydeco combination, researchers said.
“The addition of the novel CFTR corrector molecule GLPG2222 on top of highly efficacious CFTR modulator treatment already given for years in patients with gating mutations was well tolerated and may bring additional benefit to patients,” Scott Bell of Prince Charles Hospital in Brisbane, Australia, and principal investigator of the study, said in a press release.
The trial, called ALBATROSS (NCT03045523), recruited 37 CF patients across Australia and Europe. All had one so-called gating mutation and one F508del mutation in the CFTR gene (the defective gene in CF patients). CFTR correctors improve the processing of the faulty CFTR protein, allowing it to reach the cell surface.
Researchers randomly gave patients GLPG2222 or a placebo in addition to their Kalydeco treatment, which they maintained during the trial. They tested two doses — 150 mg and 300 mg — of GLPG2222.
Study results showed that while patients on Kalydeco — a drug developed by Vertex Pharmaceuticals — and a placebo increased their sweat chloride content (a marker of CFTR activity) during the 29 days of treatment, those receiving GLPG2222 significantly lowered their levels. Patients receiving the higher dose showed the best results.
The combo treatment also improved lung function — measured as percent predicted forced expiratory volume during one second (FEV1)— by 2.2 percent in the high-dose group.
Meanwhile, the treatment was well tolerated and no patient had severe adverse events. Mild adverse events reported were mostly typical for a CF patient group, researchers said. No adverse events caused patients to quit the study.
“The ALBATROSS results are the first results demonstrating that GLPG2222 is well tolerated in CF patients. In addition, the exposures achieved, coupled with the activity observed, support our dose selection plans for the investigational triple combination therapy,” said Piet Wigerinck, chief scientific officer of Galapagos. “We are impressed with the magnitude of the effects we saw on sweat chloride and FEV1 in patients whose treatment with ivacaftor has been optimized following years of therapy.”