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 was to evaluate the efficacy, effects on selected biomarkers, safety and tolerability, and pharmacokinetics of GLPG0974 in 45 ulcerative colitis patients. In this Phase 2 study, GLPG0974 was safe and well tolerated and showed two relevant biomarket effects.  These biomarker reductions did not result in a clinical improvement within 4 weeks.  Galapagos is performing subgroup analyses, considering additional indications, and discussing further development of GLPG0974 with partners.

Related publications

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The FFA2 antagonist GLPG0974: a promising approach to treat neutrophil-driven inflammation
Frédéric Vanhoutte, Florence Namour, Sonia Dupont, Mathieu Pizzonero, Steve De Vos, Laurent Sanière, Annegret Van der Aa, Johan Beetens, Gerben van 't Klooster
DDW 2014

blocks.png The FFA2 antagonist GLPG0974: opportunity to treat neutrophil-driven inflammation
F. Vanhoutte, F. Namour, S. Dupont, W. Haazen, M. Petkova, A. Van der Aa, G. van 't Klooster, J. Beetens
ECCO 2013


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The FFA2 antagonist GLPG0974: opportunity to treat neutrophil-driven inflammation
F. Vanhoutte, F. Namour, S. Dupont, D. Polancec, W. Haazen, M. Petkova, A. Van der Aa, G. van 't Klooster, J. Beetens
UEGW 2013

blocks.png GLPG0974, a selective FFA2 antagonist: a promising approach for the treatment of
neutrophil-driven disorders

Johan Beetens
ASPET Annual Meeting 2013

 
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