Cytokine Signalling Forum

Publications





December 18

Influence of Age and Renal Impairment on the Steady State Pharmacokinetics of Filgotinib, a Selective JAK1 Inhibitor

Namour F, Fagard L, Van der AA, Harrison P, Xin Y, Tasset C.
Br J Clin Pharmacol 2018 Dec;84(12):2779-2789. DOI:10.1111/bcp.13726

Age and renal impairment (RI) had limited impact on the pharmacokinetics (PK) of filgotinib (FIL) but, in subjects with severe RI, exposure to the FIL metabolite was increased. FIL is a selective JAK1 inhibitor that is extensively, rapidly and proportionately absorbed after oral dosing from 50–200mg. Its major metabolite has a similar JAK1 selectivity profile but with reduced potency. In humans, exposure to the metabolite is higher by approximately 16–20 fold compared with the pare...

Keywords: JAK, Filgotinib, Preclinical, PK-PD

November 18

Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Psoriatic Arthritis (EQUATOR): Results from a Randomised, Placebo-controlled, Phase 2 Trial

Mease P, Coates LC, Helliwell PS, Stanislavchuk M, Rychlewska-Hanczewska A, Dudek A, Abi-Saab W, Tasset C, Meuleners L, Harrison P, Besuyen R, Van der Aa A, Mozafarian N, Greer JM, Kunder R, Van den Bosch F, Gladman DD.
Lancet. 2018 Dec 1;392(10162):2367-2377. DOI 10.1016/ S0140-6736(18)32483-8

In this first clinical trial of filgotinib in patients with PsA, filgotinib was effective in treating the signs and symptoms of active PsA across various disease manifestations. The EQUATOR trial was a randomized, double-blind, placebo-controlled, Phase 2 trial, that enrolled 191 adult patients from 25 sites in seven countries. Patients with active moderate-to-severe PsA and an insufficient response or intolerance to at least one csDMARD were assigned 1:1 to receive filgotinib 200 mg or placebo...

Keywords: JAK, Filgotinib, Clinical, Phase 2

April 18

Effect of Filgotinib, a Selective JAK1 Inhibitor, with or without Methotrexate in Patients with Rheumatoid Arthritis: Patient-Reported Outcomes

Genovese MC, Westhovens R, Meuleners L, van der Aa A, Harrison P, Tasset C, Kavanaugh A.
Arthritis Res Ther 2018; 20(1):57 doi: 10.1186/s13075-018-1541-z

Patient-reported outcomes (PROs) from two, Phase 2b, filgotinib (FIL) studies, DARWIN 1 and 2, revealed that patients receiving FIL had improved and sustained PRO responses compared with placebo. With suboptimal RA treatment, patients lose joint functional ability, which heavily influences patient quality of life. The previously reported data from the DARWIN studies, concluded that patients given FIL achieved clinically relevant dose-dependent improvements compared with patients given placebo&s...

Keywords: JAK, Filgotinib, Clinical, PRO

July 17

Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective Janus kinase 1 Inhibitor, after Short-term Treatment of Rheumatoid Arthritis: Results of Two randomized Phase IIA Trials

Vanhoutte F, Mazur M, Voloshyn O, Stanislavchuk M, Van der Aa A, Namour F, Galien R, Meuleners L, van ‘t Klooster G.
Arthritis Rheumatol. 2017 Oct;69(10):1949-1959. doi: 10.1002/art.40186

In two 4-week exploratory Phase 2a trials in MTX-inadequate responder (IR) patients with RA, the highly selective JAK1 inhibitor filgotinib met the primary endpoint of ACR20 at Week 4, showing greater response than placebo. Study 1, a proof-of-concept study, included 127 patients randomised to placebo, filgotinib 100 mg BID or filgotinib 200 mg QD. Study 2, was a dose-ranging study and included 91 patients randomised to placebo, filgotinib 30 mg QD, filgotinib 75 mg QD, filgotinib 150 mg QD or ...

Keywords: JAK, Filgotinib, Clinical, Phase 2

June 17

Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)

A Kavanaugh, J Kremer, L Ponce, R Cseuz, O V Reshetko, M Stanislavchuk, M Greenwald, A Van der Aa, F Vanhoutte, C Tasset and P Harrison.
Ann Rheum Dis 2017;76:1009–19

In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX. DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or 200 mg daily in DARWIN 1 or any ...

Keywords: JAK, Filgotinib, Clinical, Phase 2

Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)

R Westhovens, P C Taylor, R Alten, D Pavlova, F Enríquez-Sosa, M Mazur, M Greenwald, A Van der Aa, F Vanhoutte, C Tasset and P Harrison.
Ann Rheum Dis 2017;76:998–100

In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX. DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or 200 mg daily in DARWIN 1 or any ...

Keywords: JAK, Filgotinib, Clinical, Phase 2

March 15

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection

Namour F, Diderichsen PM, Cox E, Vayssière B, Van der Aa A, Tasset C, Van't Klooster G.
Clin Pharmacokinet. 2015 Feb 14. [Epub ahead of print]

Filgotinib (GLPG0634) is a selective inhibitor of JAK1 currently in development for the treatment of RA and Crohn’s disease. This paper describes the pharmacokinetics of filgotinib and its active metabolite, as well as the PK/PD modelling to support dose selection for phase IIB. Two phase I, randomised, double-blind, placebo-controlled trials in healthy volunteers and one phase IIa proof-of-concept study in RA patients were used to evaluate single and multiple doses of filgotinib. Resul...

Keywords: JAK, Filgotinib, Preclinical, PK-PD

October 13

Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases

Van Rompaey L, Galien R, van der Aar EM, et al.
Journal of Immunology 2013;191:3568–77

JAK inhibitors have been identified as having a critical role as therapeutic targets for autoimmune, inflammatory and oncological diseases. GLPG0634 was shown to inhibit JAK1/JAK2 but with a much greater effect on JAK1, a critical pathway in the signal transduction of many inflammatory cytokines. In rodent testing, GLPG0634 showed significant dose-dependent reduction in disease progression in collagen-induced arthritis models, with comparable efficacy to etanercept. An orally bioavailable treatm...

Keywords: JAK, Filgotinib, Preclinical