GLPG0974 - inflammation
GLPG0974 is an orally available small molecule that reduces migration of neutrophils, one of the critical cell types in inflammatory processes, by potent inhibition of FFA2 (free fatty acid receptor 2, formerly known as GPR43). Overactivity of neutrophils is a cause of tissue damage in illnesses such as inflammatory bowel disease. A reduction of neutrophil activation and migration by inhibition of FFA2 may provide for a novel anti-inflammatory treatment approach. By inhibiting FFA2, GLPG0974 prevents free fatty acid-induced activation and migration of neutrophils towards an inflammatory site, such as in the gut of patients with inflammatory bowel disease. GLPG0974 is the first inhibitor of FFA2 to be evaluated clinically.
In the First-in-Human Phase 1 study encouraging safety data showed no relevant safety findings, including adverse events, changes in vital signs or laboratory parameters. The favourable PK profile and the highly significant changes in neutrophil biomarkers are consistent with once- or twice-daily oral dosing.
Galapagos started a second Phase 1 study in October 2012. In this clinical study, the safety and tolerability of GLPG0974 was evaluated for 2 weeks in 32 healthy volunteers. The study confirmed that GLPG0974 was safe and well tolerated at all dose levels. A dose dependent inhibition of neutrophil activation was shown, up to a maintained 24-hour inhibition of the biomarker.
In April 2013 Galapagos announced the start of the first Phase 2 clinical study with GLPG0974 in ulcerative colitis. The aim is to evaluate the efficacy, effects on selected biomarkers, safety and tolerability, and pharmacokinetics of GLPG0974 in patients. The study is anticipated to complete by year end and deliver top line data by Q1 2014.
Related posters, presentations and publications
The FFA2 (GPR43) antagonist GLPG0974: opportunity to treat neutrophil-driven inflammation
J. Beetens, F. Vanhoutte, F. Namour, S. Dupont, K. Oreskovic, D. Polancec, W. Haazen, M. Petkova, D. Van Bockstaele, A. Van der Aa, G. van 't Klooster
Knowledge for Growth 2013
GLPG0974, a selective FFA2 antagonist: a promising approach for the treatment of
ASPET Annual Meeting 2013