Introduction

The QUASAR program (NCT04033445) evaluated guselkumab (GUS), a dual-acting interleukin (IL)-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64 (a receptor on cells that produce IL-23), in patients (pts) with moderately to severely active ulcerative colitis (UC). Induction Week 12 (Week I-12) nonresponders to intravenous (IV) GUS received subcutaneous (SC) GUS through Week I-24.¹ Week I‑24 responders were eligible for maintenance therapy. Here, we present the efficacy and safety of maintenance SC GUS among GUS Week I-24 responders.

Aims & Methods

Pts who were not in clinical response (see Table for definition) at Week I-12 after IV GUS 200 mg or 400 mg received SC GUS 200 mg at Weeks I-12, I-16, and I-20. Those who were in clinical response at Week I-24 (GUS Week I-24 responders) received SC GUS 200 mg every 4 weeks during the maintenance study in a blinded fashion and were evaluated as part of the nonrandomized study population. Clinical, symptomatic, endoscopic, histologic, and patient-reported outcome measures at maintenance Week 44 (Week M-44) and safety throughout the maintenance study are reported for GUS Week I-24 responders.

Results

Overall, 123 of 203 (60.6%) Week I-12 nonresponders to IV GUS achieved clinical response at Week I-24 and entered the maintenance study phase. Induction baseline characteristics of GUS Week I-24 responders were: 74.8% had severe disease (modified Mayo score 7-9), 77.2% had a Mayo endoscopy subscore of 3, median C-reactive protein was 5.0 mg/L (upper limit of normal, 3 mg/L), and 59.3% had a history of inadequate response or intolerance to biologic or Janus kinase inhibitor therapy for UC. At Week M‑44, 67.5% of the pts maintained clinical response and 30.1% were in clinical remission. Additional efficacy outcomes are shown in the Table. The proportion of GUS Week I-24 responders in symptomatic remission (defined as a stool frequency subscore of 0 or 1 and not increased from induction baseline, and a rectal bleeding subscore of 0) at maintenance baseline (58.5%) was sustained through Week M‑44 (56.9%). Adverse events (AEs) were reported for 78.0% of GUS Week I-24 responders, serious AEs for 5.7%, and serious infections for 1.6%. No opportunistic infections or deaths occurred. No new safety concerns were identified.

Conclusion

In this refractory population of GUS Week I-24 responders, maintenance treatment with GUS provided clinical benefit across a range of clinically relevant efficacy endpoints. Safety results were consistent with the overall population and safety profile of GUS in its approved indications.

References

1. Bressler B, et al. Am J Gastroenterol. 2023;118(10S):806-807.

Disclosure

D. T. Rubin: research funding from Takeda; consultant to AbbVie, Altrubio, Allergan, Arena, Aslan, Athos, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corp/Syneos, Connect, GalenPharma/Atlantica, Genentech/Roche, InDex, Ironwood, Iterative Scopes, Janssen, Lilly, Pfizer, Prometheus, Reistone, Takeda, and Techlab; and co-founder of Cornerstones Health.
A. Dignass: fees for participation in clinical trials, review activities (data monitoring boards, statistical analysis, endpoint committees) from Abivax, AbbVie, Bristol Myers Squibb, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Roche, Sandoz, Stada, Takeda, Tillotts, and Vifor Pharma; payment for lectures/speaker’s bureaus from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Sandoz, Takeda, Tillotts, and Vifor Pharma; payment for manuscript preparation from Abbvie, Falk Foundation, Janssen, Takeda, Thieme, and UniMed Verlag.
J. R. Allegretti: consultant for AbbVie, Adiso, Ferring, Finch, Iterative Scopes, Janssen, Merck, Pfizer, Roivant, and Seres Therapeutics; speaker for AbbVie, Bristol Myer Squibb, and Janssen; and research support from Janssen, Merck, and Pfizer.
Y. Rayyan: fees for participating in clinical trials for Janssen as principal investigator and payment from lectures including service on speaker’s bureaus from Janssen, AbbVie, and Amgen.
M. Saruta: grants or contracts from Mochida, Zeria Pharma, EA Pharma, Kissei, and EPS Corporation; and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from AbbVie GK, Janssen, Mitsubishi Tanabe Pharma, Takeda, EA Pharma, Gilead Sciences, and Kissei.
D. Balderramo: advisor/speaker fees from AbbVie, Janssen, Pfizer, Takeda, and Amgen; and travel/congress support from AbbVie, Janssen, Takeda, and Ferring.
B. Bressler: advisor/speaker for AbbVie, Bristol Myers Squibb, Ferring, Janssen, Merck, Novartis, Organon, Pfizer, Sandoz, and Takeda; advisor for Alimentiv, Allergan, Amgen, AMT, Bausch Health, Bristol Myers Squibb, Celgene, Celltrion, Eupraxia Fresenius Kabi, Genentech/Roche, Gilead, Iterative Scopes, Jamp, Merck, Microbiome Insights, Mylan, Pendopharm, Protagonist, and Viatris; research support from AbbVie, Amgen, Business Intelligence, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Janssen, Merck, and Qu Biologic; and holds stock options in Qu Biologic.
L. Peyrin-Biroulet: consultant for AbbVie, Abivax, Alimentiv, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Bristol Myers Squibb, Celltrion, Connect, Cytoki, Lilly, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech/Roche, Gilead, Gossamer Bio, GlaxoSmithKline, HAC-Pharma, IAG, InDex, Inotrem, Janssen, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, and Ysopia; grants from Celltrion, Fresenius Kabi, and Takeda; honorarium for lectures from AbbVie, Amgen, Arena, Biogen, Celltrion, Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Janssen, Medac, MSD, Pfizer, Sandoz, Takeda, Tillots, Viatris, and Vifor; and fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio.
T. Hisamatsu: grant support from AbbVie, Daiichi-Sankyo, EA Pharma, JIMRO, Mitsubishi Tanabe Pharma, Mochida, Nippon Kayaku, Pfizer, and Takeda; consulting fees from EA Pharma, Janssen Research & Development, Gilead Sciences, Lilly, and Bristol Myers Squibb; and lecture fees from AbbVie, EA Pharma, Mitsubishi Tanabe Pharma, Takeda, Mochida, and Kissei.
S. Yarandi, K.-H. G. Huang, M. Germinaro, J. Zhan, and H. Zhang: employees of Johnson & Johnson and own company stock/stock options.

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)

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

1. Feagan BG et al. Lancet 2021;397:2372–84.
2. 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.