Filgotinib is a highly selective JAK1 inhibitor discovered and developed by Galapagos using its target and drug discovery technology platform. In more than 700 patient years of rheumatoid arthritis (RA) clinical study experience, filgotinib has shown a rapid onset of action, potentially best-in-class efficacy and to be safe and well tolerated in these so called DARWIN studies. A Phase 3 program with filgotinib in rheumatoid arthritis will be initiated mid-2016.
Filgotinib has also shown to be effective and safe as once-daily, oral induction treatment in moderate to severe Crohn’s disease, based on the FITZROY phase 2 study at 10- and 20-week analysis. The study achieved the primary endpoint of clinical remission at 10 weeks: the percentage of patients achieving a CDAI score lower than 150 was significantly higher in patients treated with filgotinib versus patients receiving placebo. Filgotinib was shown to be well tolerated throughout the FITZROY study, strengthening its favorable safety profile.
"We are pleased by the outcome of the FITZROY study, positioning filgotinib as a potential oral treatment for patients with Crohn’s disease. We are proud to be advancing what could become the first new oral treatment for Crohn’s disease in decades," said Piet Wigerinck, CSO of Galapagos. “These findings complement the excellent DARWIN data in rheumatoid arthritis and open up new opportunities in a broader range of inflammatory diseases for filgotinib."
In December 2015, Galapagos and Gilead signed a global partnership for the global development and commercialization of filgotinib in inflammatory diseases. Under the terms of the agreement, the companies will collaborate jointly on the global development of filgotinib starting with the initiation of Phase 3 trials in RA and Crohn's disease. Galapagos will co-fund 20 percent of global development activities and Gilead will be responsible for manufacturing and worldwide marketing and sales activities. Galapagos has the option to co-promote filgotinib in the UK, Germany, France, Italy, Spain, Belgium, the Netherlands and Luxembourg, in which case the companies will share profits equally. If Galapagos exercises its option to co-promote in Belgium, the Netherlands or Luxembourg, it will also book sales in these countries. Galapagos will receive an upfront license fee of $300 million and Gilead will make a $425 million equity investment in Galapagos. Galapagos is eligible to receive further development, regulatory and commercial milestone payments up to $1.35 billion, plus tiered royalties on global sales starting at 20%, with the exception of the co-promotion territories where profits will be shared equally.
Filgotinib (GLPG0634), an Oral JAK1 Selective Inhibitor Is Effective in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: Results from a Phase 2B Dose Ranging Study, ACR 2015
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
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.