2162: Safety and Efficacy of Filgotinib: An Update from the DARWIN 3 Phase 2 Long-term Extension with a Maximum of 8.2 Years of Exposure

René Westhovens¹, Rieke Alten², Lorenzo Dagna³, Arthur Kavanaugh⁴, Kevin Withrop⁵, Jane Barry⁶, Robin Besuyen⁷, Claudio Corallo⁸, Dick de Vries⁹, Nicolas Martin¹⁰, Chris Watson⁶, Mark C. Genovese¹¹, Alberto Spindler¹², Mykola Stanislavchuk¹³, Maria Greenwald¹⁴ and Paul Emery¹⁵, ¹Department of Rheumatology, KU Leuven, Skeletal Biology and Engineering Research Center, Leuven, Belgium, ²Department of Internal Medicine and Rheumatology, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany, ³Department of Internal Medicine, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy, ⁴Division of Rheumatology, Allergy, and Immunology, University of California San Diego, La Jolla, CA, ⁵Oregon Health & Science University, Schools of Medicine and Public Health,, Portland, OR, ⁶Medical Affairs, Galapagos Biotech Ltd., Cambridge, United Kingdom, ⁷Clinical Development, Galapagos BV, Leiden, Netherlands, ⁸Medical Affairs, Galapagos Biopharma Italy S.R.L., Milan, Italy, ⁹Research and Development, Clinical Research, Galapagos BV, Leiden, Netherlands, ¹⁰Biostatistics, Galapagos NV, Mechelen, Belgium, ¹¹Clinical Development, Gilead Sciences Inc., Foster City, CA, ¹²Rheumatology Section, Centro Medico Privado de Reumatologia, San Miguel de Tucuman, Argentina, ¹³Rheumatology, National Pirogov Memorial Medical University, Vinnytsia, Ukraine, ¹⁴Rheumatology, Desert Medical Advances, Palm Desert, CA, ¹⁵Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Background/Purpose: DARWIN 3 (NCT02065700) is a long-term extension (LTE) study assessing the safety and efficacy of filgotinib (FIL) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX).¹ In the DARWIN 1 (NCT01888874) and DARWIN 2 (NCT01894516) parent studies, patients received FIL in combination with MTX or FIL monotherapy, respectively. This analysis aimed to provide an update on the safety and efficacy of FIL 200 mg (FIL200) in patients with RA, with or without MTX, with a maximum of 8.2 years of exposure.

Methods: Patients completing the DARWIN 1 (FIL + MTX) and DARWIN 2 (FIL monotherapy) Phase 2 studies could enter DARWIN 3, receiving FIL200. The proportion of patients experiencing treatment-emergent adverse events (TEAEs) were reported using the safety analysis set, comprising data from both the parent and LTE studies. Efficacy was assessed from LTE baseline using the American College of Rheumatology (ACR) 20/50/70 improvement criteria and Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), up to 264 weeks. Low disease activity and remission were defined as DAS28-CRP ≤ 3.2 and < 2.6, respectively.

Results: In total, 739 patients were enrolled in DARWIN 3. Mean (standard deviation; SD) FIL exposure was 4.89 (2.72) years in the FIL + MTX group and 4.78 (2.79) years in the FIL monotherapy group. In the FIL + MTX vs FIL monotherapy groups, TEAEs were reported for 90.9% and 92.1% of patients, respectively (Table). The most common TEAE was infection. In both treatment groups, 8 patients had a TEAE leading to death (1.6% and 3.3%, respectively). Exposure-adjusted incidence rates, censored at time of first event for major adverse cardiovascular event, venous thromboembolism, herpes zoster, infections, serious infections, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, gastrointestinal perforations and TEAEs leading to death, will be reported. Through 5 years, ACR20/50/70 responses were maintained in 86.3%/66.7%/50.7% of the FIL + MTX group and 90.8%/74.8%/51.4% of the FIL monotherapy group, respectively (observed data). DAS28-CRP low disease activity and remission rates (nonresponder imputation) at DARWIN 3 baseline were 46.1%/40.1% (FIL + MTX) and 29.6%/24.8% (FIL monotherapy) (Figure). At Week 264, the proportion of patients achieving low disease activity and remission were 34.0%/34.3% (FIL + MTX) and 27.0%/24.8% (FIL monotherapy).

Conclusion: With a maximum of 8.2 years of exposure in patients with RA, the FIL safety profile is similar between the background MTX and monotherapy treatment arms. Both arms show sustained efficacy over time.

Reference:
1. Kavanaugh A, et al. J Rheumatol 2021;48:1230–8






R. Westhovens: Celltrion, 2, 6, Galapagos, 2, 6, Gilead, 2, 6; R. Alten: AbbVie, 2, 6, Amgen, 2, 6, Biogen, 2, 6, BMS, 2, 6, Celltrion, 2, 6, Gilead, 2, 6, Janssen, 2, 6, Lilly, 2, 6, Medac, 2, 6, MSD, 2, 6, Mylan, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, Roche, 2, 6, Sandoz, 2, 6, Sanofi-Genzyme, 2, 6, UCB, 2, 6, Viatris, 2, 6; L. Dagna: AbbVie, 2, AstraZeneca, 2, Biogen, 2, BMS, 2, 5, Boehringer Ingelheim, 2, Celltrion, 5, Eli Lilly, 2, Galapagos, 2, GSK, 1, Janssen, 2, Kiniksa Pharmaceuticals, 2, 5, Novartis, 2, 6, Pfizer, 2, 5, Sobi, 2, 5, 6; A. Kavanaugh: Amgen, 2, BMS, 2, Eli Lilly, 2, Novartis, 2, Pfizer, 2, UCB, 2; K. Withrop: AbbVie, 2, AstraZeneca, 2, BMS, 2, 5, Eli Lilly, 2, Galapagos, 2, Gilead, 2, GSK, 2, Novartis, 2, Pfizer, 2, 5, Regeneron, 2, Roche, 2, Sanofi, 2, UCB, 2; J. Barry: Galapagos, 3, 11; R. Besuyen: Galapagos, 3, 11; C. Corallo: Galapagos, 3, 11; D. de Vries: Galapagos, 3, 11; N. Martin: Galapagos, 7; C. Watson: Galapagos, 3, 11; M. Genovese: Gilead, 3, 11; A. Spindler: None; M. Stanislavchuk: Amgen, 5, AstraZeneca, 5, Celgene, 5, Eli Lilly, 5, Galapagos, 5, Gilead, 5, Human Genome, 5, Janssen, 5, MSD, 5, Nichi-Iko Pharmaceutical, 5, Pfizer, 5, Roche, 5; M. Greenwald: AbbVie, 5, Aclairs, 5, Eli Lilly, 5, Galapagos, 5, Janssen, 5, Nimbus, 5; P. Emery: Boehringer Ingelheim, 2, Eli Lilly, 2, Novartis, 2.