FIlgotinib (GLPG0634) is an orally-available, selective inhibitor of JAK1 (Janus kinase 1) being developed by Galapagos for the treatment of rheumatoid arthritis and potentially other inflammatory diseases. JAKs are critical components of signaling mechanisms utilized by a number of cytokines and growth factors, including those that are elevated in rheumatoid arthritis (RA) patients. JAK inhibitors have shown long-term efficacy in RA trials with an early onset of action.
In November 2011 Galapagos announced that filgotnib achieved the primary endpoint (ACR20) of significant improvement in the signs and symptoms of rheumatoid arthritis at four weeks in a single center study. 83% of patients receiving filgotinib reached the ACR20 score and half of the treated patients went into either disease remission or low disease activity. Furthermore, this compound showed a unique safety profile, with a clean profile on LDL/cholesterol and no anemia observed. In a second Phase 2, dose-range finding clinical trial in multiple centers reported in November 2012, Filgotinib repeated the excellent safety of the drug, as well as the clinical benefit to RA patients within 4 weeks. Clinical improvements were seen in RA patients with once-daily dosages of 75-300mg.
Galapagos started a Phase 2B clinical program with filgotinib in June 2013. The DARWIN Phase 2B program includes two dose finding studies and an open label extension study. The dose finding studies evaluates the efficacy and safety of filgotinib with 24 weeks of treatment in 875 moderate to severe RA patients refractory to methotrexate. Galapagos reported 12-week topline data from the DARWIN 1 program in April 2015 and from the DARWIN 2 program in April 2015. Filgotinib is the first selective JAK1 inhibitor in development for RA, and this strategy could result in a cleaner safety profile than other JAK inhibitors.
In January 2014, Galapagos started a Phase 2 study with filgotinib in Crohn's disease. This study will evaluate the efficacy and safety of filgotinib during 20 weeks of treatment in 180 patients with active Crohn's disease. Galapagos expects to read out topline results in Q2 2015.
On 29 February 2012 Galapagos signed a global agreement with AbbVie to develop and commercialize filgotinib. For more information about the deal, read the press release.
On 17 May 2013 Galapagos announced an extension of their GLPG0634 clinical development collaboration to include Crohn's disease. For more information about the extension, read the press release.
Dose selection of GLPG0634, a selective JAK1 inhibitor, for rheumatoid arthritis Phase 2B studies: PK/PD modeling of pSTAT1 biomarker and DAS28 clinical response
Florence Namour, Paul Mathias Diderichsen, Eugène Cox, Chantal Tasset and Gerben van 't Klooster
GLPG0634m1, a major metabolite of the JAK1-selective inhibitor GLPG0634, is also JAK1-selective and efficient in the rat CIA model
Cécile Belleville-Da Costa, Didier Merciris, Béatrice Vayssière, Nicolas Houvenaghel, Alain Monjardet, Liên Lepescheux, Sonia Dupont, Thierry Christophe, Monica Borgonovi, Philippe Clément-Lacroix, Christel Menet, Luc Van Rompaey, Reginald Brys, René Galien
GLPG0634, a selective JAK1 inhibitor, confirms its low liability for drug-drug interactions
F. Namour, J. Desrivot, A. Van der Aa, C. Tasset, G. van 't Klooster
Exploration of GLPG0634, the first selective JAK1 inhibitor, in inflammatory Bowel Disease is supported by early clinical results and mouse DSS-colitis data
René Galien, Didier Merciris, Frédéric Vanhoutte, Carole Delachaume, Florence Namour, Béatrice Vayssière, Annegret Van der Aa, Reginald Brys, Gerben van 't Klooster
GLPG0634, The First Selective JAK1 Inhibitor, Shows Strong Activity in the Mouse DSS-Induced Colitis Model
Didier Merciris, Carole Delachaume, Veerle De Vriendt, Anne-Laure Boutet, Laetitia Perret, Marie-Christine Ceccotti, Steve De Vos, Alain Monjardet, Reginald Brys and René Galien
An Active Metabolite Contributes to the Pharmacodynamics and Efficay of GLPG0634, a Selective JAK1 Inhibitor
Florence Namour, René Galien, Frédéric Vanhoutte, Piet Wigerinck and Gerben van 't Klooster
The JAK1-Selective Inhibitor GLPG0634 is Safe and Rapidly Reduces Disease Activity in Patients with Moderate to Severe Rheumatoid Arthritis; Results of a 4-Week Dose Ranging Study
Chantal Tasset, Pille Harisson, Annegret Van der Aa, Luc Meuleners, Frédéric Vanhoutte and Gerben van 't Klooster
Analysis of the JAK1 Selectivity of GLPG0634 and its Main Metabolite in Different Species, Healthy volunteers and Rheumatoid Arthritis Patients
René Galien, Béatrice Vayssière, Steve de Vos, Marielle Auberval, Nick Vandeghinste, Sonia Dupont, Philippe Clément-Lacroix, Philippe Delerive, Frédéric Vanhoutte, Reginald Brys, Annegret Van der Aa, Luc van Rompaey and Gerben van 't Klooster
Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases
Luc van Rompaey, René Galien, Ellen M. van der Aar, Philippe Clément-Lacroix, Luc Nellen, Bart Smets, Lien Lepescheux, Thierry Christophe, Katja Conrath, Nick Vandeghinste, Béatrice Vayssière, Steve de Vos, Stephen Fletcher, Reginald Brys, Gerben van 't Klooster, Jean H. M. Feyen and Christel Menet
J. Immunol. 2013 Oct 1;191(7):3568-77
Once-daily dosing of GLPG0634, a selective JAK1 inhibitor, is supported by its active metabolite
Florence Namour, René Galien, Frédéric Vanhoutte, Annegret Van der Aa, Chantal Tasset, Piet Wigerinck and Gerben van 't Klooster
Biological effects of the JAK1 selective inhibitor GLPG0634 on inflammation markers in arthritic mice
Béatrice Vayssière, Steve de Vos, Didier Merciris, Marielle Auberval, Sonia Dupont, Nick Vandeghinste, Lien Lepescheux, Philippe Clément-Lacroix, Philippe Delerive, Luc van Rompaey, Reginald Brys, and René Galien
Advances in the Discovery of Selective JAK Inhibitors
Christel J. Menet, Luc Van Rompaey, Raphaël Geney
Prog Med Chem. 2013;52:153-223
Selective JAK1 Inhibition in the Treatment of Rheumatoid Arthritis: Proof of Concept with GLPG0634
F. Vanhoutte, MDM. Mazur, A. Van der Aa, P. Wigerinck, G. van ’t Klooster
Once-daily High Dose Regimens of GLPG0634 in Healthy Volunteers are Safe and Provide Continuous Inhibition of JAK1 but not JAK2
Florence Namour, René Galien, Lien Gheyle, Frédéric Vanhoutte, Béatrice Vayssière, Annegret Van der Aa, Bart Smets and Gerben van 't Klooster
Efficacy and safety of GLPG0634, a selective JAK1 inhibitor, after short-term treatment of rheumatoid arthritis; results of a phase IIA trial
F. Vanhoutte, et al.
The JAK1 inhibitor GLPG0634 is efficacious and safe in rheumatoid arthritis patients Gerben Van 't Klooster, et al.
Knowledge for Growth 2012
GLPG0634 Shows Selective Inhibition of JAK1 and Maintained JAK-STAT Suppression in Healthy Volunteers
F. Vanhoutte, et al.
Preclinical and early clinical evaluation of GLPG0634, a selective JAK1 inhibitor for the treatment of rheumatoid arthritis
G. Van 't Klooster, et al.
GLPG0634, a Janus kinase inhibitor for the treatment of rheumatoid arthritis
L. Van Rompaey, et al.