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
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 filgotinib 300 mg QD.
Filgotinib showed greater ACR20 response at Week 4 compared with placebo; this reached statistical significance in Study 1, but not Study 2. After 4 weeks, filgotinib had a
dose-dependent effect on circulating biomarkers – reduced levels with increasing dose.
Early side effects seen with other JAK inhibitors were not seen, and no relevant abnormalities in serum biochemistry were reported. The observed efficacy and safety of filgotinib provides initial evidence that selective JAK1 inhibition may be a future way to treat RA.