GLPG1837 is a clinical-stage investigational treatment for cystic fibrosis (CF) being developed by Galapagos in collaboration with Abbvie.

How GLPG1837 works

CF is an inherited progressive condition in which there is a build-up of thick, sticky mucus in the lungs and other organs. The condition is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that carries the information necessary to make the CFTR protein.

The normal CFTR protein functions at the cell membrane as a gated passageway that maintains the flow of chloride ions and water in and out of cells. Mutations in the CFTR gene affect the movement of chloride ions and water resulting in the production of thick, sticky mucus, which is the main characteristic of CF.

CFTR mutations are grouped into five classes based on the defect they cause to the CFTR protein and the faulty CFTR proteins may hinder the normal flow of the salts and water in and out of cells in multiple ways.

CFTR modulators are a specialized class of CF therapeutics that address the underlying cause of CF. GLPG1837 is one such CFTR modulator.

The so-called class 3 CFTR mutations are known to lead to the production of CFTR proteins with gating problems. In other words, such CFTR protein variants tend to close the passage gates blocking the movement of chloride ions and water. Class 4 CFTR mutations generate structurally correct CFTR proteins, but with conductance issues, i.e., they are unable to maintain the flow of water and ions across the membrane.

GLPG1837 is a CFTR potentiator — a type of CFTR modulator that helps keep the gated passageway open for extended periods and facilitate the movement of chloride ions across the cell membrane.

Research has shown that GLPG1837 is beneficial in class 3 mutations, e.g., G551D, G178R, and S549N. Furthermore, it also has been shown to alleviate the CFTR defect caused by a class 4 mutation, R117H.

GLPG1837 in clinical trials

A clinical trial (NCT02707562) called SAPHIRA 1 compared the effectiveness of three increasing doses of GLPG1837 in improving the function of the CFTR protein in CF patients with G551D mutations. This Phase 2 trial included 26 CF patients, age 18 or older. Twenty-five patients who were on Kalydeco (ivacaftor) before the trial, underwent a one-week washout period before the start of GLPG1837 treatment.

During the four-week study, patients received an initial dose of 125 mg of GLPG1837 twice daily for one week. The dose was increased to 250 mg for the next seven days. They received 500 mg of GLPG1837 for the final two weeks of the study. Patients were monitored for up to nine weeks to record any response to the treatment.

Sweat chloride concentration was measured as an indicator of the CFTR ion channel function. Results showed there was a significant decrease in patients’ sweat chloride concentration, with the most marked difference observed with 500 mg of GLPG1837 treatment. The levels reduced to 66 mmol/L at nine weeks compared to 98 mmol/L at the start of the study (baseline). GLPG1837 treatment also restored lung function to the levels of Kalydeco treatment, the study found.

In the SAPHIRA 2 study (NCT02690519), the effect of two sequentially administered doses of GLPG1837 were evaluated in CF patients with the S1251N mutation. A total of seven patients, age 18 to 51, were included in this study. Similar to SAPHIRA 1, patients on Kalydeco underwent a washout period of one week before starting the treatment. Patients received 62.5 mg of GLPG1837 twice a day for the first 14 days followed by 125 mg twice a day for the remaining 14 days.

Results similar to SAPHIRA 1 were reported in this study; there was a significant reduction in sweat chloride concentration in a dose-dependent manner, especially at the 125 mg dose. Lung function was regained and stable after GLPG1837 treatment. However, the small number of participants in the study (seven) was a limitation and could affect the interpretations, the researchers noted.

In both studies, GLPG1837 was found to be well-tolerated and generally safe.

Other information

A triple combination treatment with GLPG1837, and two other experimental CFTR modulatorsGLPG2222 and GLPG2665, has shown promising results in pre-clinical studies. This triple combo therapy is expected to work for 80 percent of all CFTR mutations seen in the CF population.

***

Cystic Fibrosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health care providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website

Vijaya Iyer is a freelance science writer with BioNews Services. She has contributed content to their several disease-specific websites, including cystic fibrosis, multiple sclerosis, muscular dystrophy, and more. She received her PhD in Microbiology from Kansas State University. Her research focused on molecular biology, bacterial interactions, metabolism, and animal models to study bacterial infections. Following her PhD, Dr. Iyer went on to complete three postdoctoral fellowships at Kansas State University, University of Miami and Temple University. She joined BioNews Services to utilize her scientific background and writing skills to help patients and caregivers remain abreast with important scientific breakthroughs.
×
Vijaya Iyer is a freelance science writer with BioNews Services. She has contributed content to their several disease-specific websites, including cystic fibrosis, multiple sclerosis, muscular dystrophy, and more. She received her PhD in Microbiology from Kansas State University. Her research focused on molecular biology, bacterial interactions, metabolism, and animal models to study bacterial infections. Following her PhD, Dr. Iyer went on to complete three postdoctoral fellowships at Kansas State University, University of Miami and Temple University. She joined BioNews Services to utilize her scientific background and writing skills to help patients and caregivers remain abreast with important scientific breakthroughs.
Latest Posts
  • cystic fibrosis guide
  • CARSTAR CFF recognition
  • orphan drug and EU
  • CMV and cystic fibrosis