THU0173 Long term safety and efficacy of filgotinib in a phase 2B open label extension study in patients with rheumatoid arthritis: results up to 144 weeks

Abstract

BackgroundFilgotinib (GLPG0634, GS-6034) is an oral JAK1 selective inhibitor with a favorable safety and efficacy profile in two 24-week Phase 2b studies as add-on to methotrexate (DARWIN 1) or as monotherapy (DARWIN 2) in patients with active rheumatoid arthritis (RA). Three daily doses were tested (50mg, 100mg or 200mg) in comparison to placebo.ObjectivesTo assess long term safety and efficacy of filgotinib 200mg daily in patients from the DARWIN 3 Phase 2 open-label extension study.MethodsPatients who completed DARWIN 1 or 2 and enrolled in DARWIN 3 received filgotinib 200mg once daily or 100mg twice daily, depending on prior treatment assignment. The DARWIN 3 data cut off was when the last patient reached extension Week 60. For safety, all data from the first intake of filgotinib in DARWIN 1/2/3 were analysed (up to 144 weeks).Results877 patients participated in DARWIN 1 or 2, 790 completed and 739 entered DARWIN 3 from 22 countries (82% females, mean age 53y). 559 patients (75.6%) completed Week 60, 9.3% discontinued due to positive Quantiferon, 7.8% due to other adverse events, 6.8% for other reasons and 0.3% due to insufficient response. Overall exposure to filgotinib was 1314 patient-years (PYE).Treatment-emergent adverse events (157.7/100PYE), serious adverse events (5.3/100PYE) and serious infections (1.9/100PYE) occurred at similar rates compared to the core studies, however infections decreased on a percentage basis from 15% (109/739, W0–12) to 5% (25/549, W85–96). 16 cases of Herpes zoster were reported (1.2/100PYE), 6 cases of malignancy (excl. NMSC) (0.5/100PYE) and 1 case of MACE (0.1/100PYE). There was no active case of tuberculosis. Three fatalities were reported (0.2/100PYE). Mean change from baseline (CFB) at Week 96 and CTCAE toxicity grading in lab parameters of special interest are shown in table 1.Table 1.Mean CFB at Week 96 and CTCAE toxicity grading of selected lab parametersMean CFBCTCAE Grade 3–4 (%) Hb+6.5 g/L0.4Neutrophils−1.73 giga/L1Lymphocytes−0.19 giga/L2Creatinine+8.2 μmol/L0ALT+6.1 U/L0.4LDL+13%–HDL+23%–Tot chol/HDL−4%–NK cells−0.02 giga/L–Based on an observed case analysis 84% (505/601), 65% (389/601), 44% (267/601) and 51% (299/587) of patients reached ACR20, ACR50, ACR70 and DAS28(CRP) remission at Week 60 respectively.ConclusionsWith 1314 patient-years of exposure, the safety profile of filgotinib appears consistent with that of previously reported double-blind studies and the clinical response appears durable.References Westhovens R et al. Ann Rheum Dis 2016;0:1–11.Kavanaugh A et al. Ann Rheum Dis 2016;0:1–11. Disclosure of InterestR. Alten Grant/research support from: Galapagos, R. Westhovens Grant/research support from: Roche, Consultant for: Galapagos, Speakers bureau: BMS, A. Kavanaugh Consultant for: Galapagos, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, M. Genovese Grant/research support from: Abbvie, Eli Lilly, Pfizer, Astellas, Vertex, Consultant for: Galapagos, Gilead, Abbvie, Eli Lilly, Pfizer, Astellas, Vertex, K. Winthrop Grant/research s...

Janus kinase inhibitors: A therapeutic strategy for cancer and autoimmune diseases

“…Results of two other Phase IIa trials showed that filgotinib is generally well‐tolerated in RA subjects that had an insufficient response to MTX (Vanhoutte et al, 2017). This study was continued by two Phase IIb trials: randomized, dose‐finding study (DARWIN1; additive to MTX) and DARWIN2 (Single therapy; Alten et al, 2017). DARWIN 1 was designed on 594 RA subjects with a poor response to MTX (Westhovens, Alten, et al, 2016).…”