Galapagos NV has announced that the selective JAK1 inhibitor filgotinib as once-daily monotherapy at week 24 showed further improvements in signs and symptoms of moderately to severe, active rheumatoid arthritis (RA) in the DARWIN 2 Phase 2B study.
Filgotinib was well tolerated in this study. Hemoglobin levels increased. These final 24-week study results are consistent with the efficacy and safety profile of filgotinib observed in prior clinical studies. With these final results, the data package for AbbVie is complete, which triggers the start of the licensing decision period.
DARWIN 2 is a 24-week, double-blind, placebo-controlled evaluation of filgotinib, as once-daily administration (QD dosing) at 3 dose levels. Results were reported for 283 patients with moderate to severe rheumatoid arthritis who showed an inadequate response to methotrexate. Filgotinib or placebo was given as monotherapy. The patients were evaluated up to 24 weeks.
The results from this study show a rapid onset of efficacy, as of week 1 for ACR and DAS28(CRP) responses. Maximum ACR20 and ACR50 responses were obtained at week 8 and week 12 respectively. Additional gain was reported for ACR70 and DAS28(CRP) during the second half of the study. In the highest dose groups, up to 50% of the patients reached low disease activity or remission. The 100 mg and 200 mg QD doses achieve similar levels of efficacy.
Over all dose groups including placebo, 3.9% of patients stopped treatment during the study for safety reasons. A higher discontinuation rate for safety was observed for placebo (5.6%) during the first 12 weeks of the study compared to filgotinib treated patients (2.5%) up to week 24. Similar incidence of serious and non-serious treatment-emergent adverse events was reported, evenly spread over the dose groups including placebo.
A higher rate of infections was observed in filgotinib (19% over 24 weeks) compared to placebo (10% up to week 12), with serious infections remaining limited (1.4% of filgotinib patients). No malignancies, TB, MACE, opportunistic infections, or death were reported. Consistent with its selective JAK1 inhibition, filgotinib treatment led to an improvement in hemoglobin (up to 0.4 g/dL, or 3.6% increase from baseline). Neutrophil levels remained stable after initial decline to mid-normal range at week 4. There was no impact on lymphocytes or liver function tests. The similar increases in LDL and HDL were maintained.
"The DARWIN 2 24-week data clearly show the efficacy of this compound in rheumatoid arthritis. In addition, the safety profile is quite notable. The increase in hemoglobin and lack of lymphocyte reduction suggest that there can be differentiation of various safety signals among different JAK inhibitors," said Professor Arthur Kavanaugh, MD, Professor of Medicine at the University of California, San Diego (UCSD) School of Medicine, and Principal Investigator for DARWIN 2.
"These final 24-week monotherapy data of DARWIN 2 confirm previous results and we believe these support the best-in-class potential of filgotinib, our oral, once a day, JAK1 selective treatment in RA," said Dr Piet Wigerinck, Chief Scientific Officer of Galapagos. "We experience a lot of enthusiasm from the medical community, to make filgotinib broadly available to patients with other inflammatory diseases. We very much look forward to Abbvie's in-licensing decision."