Introduction
Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC). FIL 200 mg (FIL200) was effective in inducing and maintaining clinical remission vs placebo (PBO) and well tolerated in patients with UC in the phase 2b/3 SELECTION trial (NCT02914522).1
Aims & Methods
We assessed the efficacy and safety of continued FIL200 therapy in the ongoing SELECTION long-term extension (LTE) study (NCT02914535). In SELECTION, adults with moderately to severely active UC received induction (IND) FIL200, FIL 100 mg (FIL100) or PBO once daily for 11 weeks. Patients in clinical remission or with a Mayo Clinic Score (MCS) response at week 10 (responders) entered the 47-week Maintenance (MNT) Study. Patients who completed IND and MNT (completers), patients who were not responders at IND week 10 (non-responders), and patients with disease worsening during MNT were eligible to enter SELECTIONLTE and receive open-label FIL200. This interim analysis assessed the efficacy and safety of open-label FIL200 through LTE week 144 in completers and LTE week 192 in non-responders, respectively. Data are shown for up to a maximum of 3.9 years of treatment each (completers: 58 + 144 weeks; non-responders 10 + 192 weeks) as of the data cut-off (24 February 2022). Partial MCS (pMCS) was reported as observed without imputation and proportions of patients achieving pMCS remission (pMCS ≤1) and IBDQ remission (score ≥170) were reported as observed and using non-responder imputation (NRI). Adverse events (AEs) and AEs of interest were evaluated using exposure-adjusted incidence rates per 100 patient-years of exposure (PYE).
Results
This analysis included 148 completers and 372 non-responders (IND FIL100, n=212; IND FIL200, n=160). Proportions of patients achieving pMCS or IBDQ remission over time (as observed and NRI) are shown in the Table. Among completers, reductions in mean pMCS in SELECTION over weeks 0–10 were maintained up to LTE week 144. In non-responders, mean pMCS decreased from LTE baseline to LTE week 192. In completers, pMCS remission was achieved by 80.0% of patients at LTE week 144, as observed. In non-responders, pMCS remission was achieved by 59.2% of patients at LTE week 192, as observed. More than 70% of completers and non-responders achieved IBDQ remission (as observed) at LTE week 144/192 and proportions were maintained over time. Safety events among all patients treated with open-label FIL200 in the LTE study (total PYE=2055.5) revealed no new safety signals.
Table. Proportions of patients achieving pMCS or IBDQ remission in SELECTION and SELECTIONLTE (observed case and NRI)
| pMCS remission % (n/N)
| IBDQ remission % (95% confidence interval); n/N
|
| Completers IND FIL200 → MNT FIL200 → LTE FIL200 (n = 148)
| Non-responders IND FIL100 → LTE FIL200 (n = 212)
| Non-responders IND FIL200 → LTE FIL200 (n = 160)
| Completers IND FIL200 → MNT FIL200 → LTE FIL200 (n = 148)
| Non-responders IND FIL100 → LTE FIL200 (n = 212)
| Non-responders IND FIL200 → LTE FIL200 (n = 160) |
Baseline Observed NRI | 0 0
| – –
| – –
| 3.4 (1.1–7.9); 5/145 3.4 (1.1–7.7); 5/148
| – –
| – –
|
Week 10 Observed NRI
| 45.6 (67/147) 45.3 (67/148)
| – –
| – –
| 68.0 (59.8–75.5); 100/147 67.6 (59.4–75.0); 100/148
| – –
| – –
|
Week 26 Observed NRI
| 67.4 (89/132) 60.1 (89/148)
| – –
| – –
| 78.2 (70.7–84.6); 115/147 77.7 (70.1–84.1); 115/148
| – –
| – –
|
Week 58/LTE baseline Observed NRI
| 72.4 (105/145) 70.9 (105/148)
| 0.5 (1/212) 0.5 (1/212)
| 1.3 (2/160) 1.3 (2/160)
| 78.5 (70.9–84.9); 113/144 76.4 (68.7–82.9); 113/148
| 16.0 (11.0–22.0); 30/188 14.2 (9.8–19.6); 30/212
| 26.8 (19.6–35.0); 37/138 23.1 (16.8–30.4); 37/160
|
LTE week 48 Observed NRI
| 75.4 (98/130) 66.2 (98/148)
| 41.9 (62/148) 29.2 (62/212)
| 44.4 (48/108) 30.0 (48/160)
| 82.0 (74.4–88.1); 109/133 73.6 (65.8–80.5); 109/148
| 63.3 (55.3–70.8); 100/158 47.2 (40.3–54.1); 100/212
| 61.9 (52.3–70.9); 70/113 43.8 (35.9–51.8); 70/160
|
LTE week 96 Observed NRI
| 83.2 (94/113) 63.9 (94/147)
| 58.2 (71/122) 33.5 (71/212)
| 64.0 (57/89) 35.6 (57/160)
| 81.5 (73.4–88.0); 97/119 66.4 (58.2–74.0); 97/146
| 71.2 (62.4–78.9); 89/125 42.0 (35.3–48.9); 89/212
| 66.3 (55.5–76.0); 59/89 36.9 (29.4–44.9); 59/160
|
LTE week 144 Observed NRI
| 80.0 (36/45) 54.5 (36/66) | 57.9 (62/107) 29.5 (62/210)
| 63.3 (50/79) 31.3 (50/160)
| 86.4 (72.6–94.8); 38/44 50.7 (38.9–62.4); 38/75
| 78.1 (69.0–85.6); 82/105 39.2 (32.6–46.2); 82/209
| 70.9 (59.6–80.6); 56/79 35.0 (27.6–42.9); 56/160
|
LTE week 192 Observed NRI
| – –
| 57.1 (24/42) 23.3 (24/103)
| 62.1 (18/29) 20.2 (18/89)
| – –
| 73.3 (58.1–85.4); 33/45 25.2 (18.0–33.5); 33/131
| 76.7 (57.7–90.1); 23/30 21.9 (14.4–31.0); 23/105
|
Conclusion
FIL200 was effective in maintaining symptomatic remission and improvements in health-related quality of life for up to ~4 years. No new safety signals were observed over ~4 years of treatment, and incidence rates of safety events were similar to those seen in previous analyses.2 Our data show that prolonged FIL treatment has a consistent and established safety profile and is efficacious for the long-term management of UC.
References
- Feagan BG et al. Lancet 2021;397:2372–84.
- Feagan BG et al. J Crohns Colitis 2022;16(Suppl1):i456–7.
Disclosure
BF reports grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; personal fees from Ablynx, ActoGeniX, Akebia Therapeutics Inc., Allergan, Atlantic Pharma, Avaxia Biologics Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, Eli Lilly, enGene, Exeliom Biosciences, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead, Given Imaging, gIcare Pharma, GlaxoSmithKline, Gossamer Bio, Inception IBD Inc., Ironwood, Japan Tobacco Company, Kyowa Hakko Kirin Co., Ltd, Lexicon, Lycera Biotech, Merck, Mesoblast Pharma, Millennium, Nestlé, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus Therapeutics and Diagnostics, Protagonist, Q32 Bio, Qu Biologics, Salix, Shire, Sienna Biologics, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts, UCB, Vertex, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand and Zyngenia; and is the Senior Scientific Director of Alimentiv Inc. and a Professor of Medicine at Western University.
KM reports personal fees from AbbVie, Bristol Myers Squibb, Celltrion, EA pharma, Eli Lilly, Gilead, Janssen Pharmaceuticals, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, Takeda and Zeria Pharmaceutical; and research grants from AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku and Takeda.
GR reports personal fees from AbbVie, AstraZeneca, Augurix, Bristol Myers Squibb, Boehringer Ingelheim, Calypso, Celgene, Dr. Falk Pharma, Ferring Pharmaceuticals, Fisher, Genentech, Gilead, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Phadia, Pierre Fabre, Roche, Takeda, Tillotts, UCB, Vifor, Vital Solutions and Zeller; and grants from AbbVie, Ardeypharm, Augurix, Calypso, Dr. Falk Pharma, Flamentera, MSD, Novartis, Pfizer, Roche, Takeda, Tillotts, UCB and Zeller.
LP-B reports personal fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, InDex Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, MSD, Mylan, Norgine, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Theravance Biopharma, Thermo Fisher Scientific, Tillotts, Viatris and Vifor; grants from AbbVie, Fresenius Kabi, MSD and Takeda; and stock options from CTMA.
MF, AO, AdH and CR and are employees and shareholders of Galapagos NV.
The SELECTION trial was sponsored by Gilead Sciences Inc (Foster City, CA, USA). The SELECTIONLTE trial was sponsored by Galapagos NV (Mechelen, Belgium), who funded these analyses.
Medical writing support for the development of this abstract was provided by Risha Bulusu, MBiochem, of PharmaGenesis London, London, UK, and was funded by Galapagos NV.