E0391 - The Effect of Guselkumab Induction Therapy on Inflammatory Biomarkers in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Results Through Week 12

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Gary Lichtenstein, MD

University of Pennsylvania
Philadelphia, PA

Gary Lichtenstein, MD¹, Axel Dignass, MD, PhD², William J. Sandborn, MD³, Kuan-Hsiang Huang, MD, PhD⁴, Matthew Germinaro, MD⁵, Rebbecca Wilson, DPH⁴, Hongyan Zhang, PhD⁴, Baili Chen, PhD⁶, Minhu Chen, PhD⁶, Tadakazu Hisamatsu, MD, PhD⁷, Brian G. Feagan, MD⁸, Julian Panés, MD⁹, Laurent Peyrin-Biroulet, MD, PhD¹⁰
¹University of Pennsylvania, Philadelphia, PA; ²Agaplesion Markus Hospital / Goethe University, Frankfurt, Hessen, Germany; ³University of California San Diego, La Jolla, CA; ⁴Janssen Research & Development, LLC, Spring House, PA; ⁵Janssen Research & Development, LLC., Spring House, PA; ⁶The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; ⁷Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ⁸Alimentiv, Inc.; Western University, London, ON, Canada; ⁹Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; ¹⁰University of Lorraine, Nancy, Lorraine, France

Introduction: C-reactive protein (CRP) and fecal calprotectin (FeCal) are non-invasive inflammatory biomarkers used to assess disease activity in patients with inflammatory bowel disease (IBD). Here we report inflammatory biomarker results through Week 12 for QUASAR (NCT04033445) Phase 2b Induction. QUASAR is a randomized, double-blind, placebo-controlled study of guselkumab (GUS), an interleukin-23 p19 subunit antagonist, in patients with moderately to severely active UC who had an inadequate response or intolerance to conventional (ie, thiopurines or corticosteroids) or advanced therapy (ie, tumor necrosis factor alpha antagonists, vedolizumab, or tofacitinib).

Methods: Patients with moderately to severely active UC (defined as a modified Mayo score of 5 to 9, inclusive with a Mayo rectal bleeding subscore ≥ 1 and a Mayo endoscopy subscore ≥ 2 obtained at baseline [BL]) were randomized 1:1:1 to receive IV GUS 200 mg, 400 mg, or placebo at Weeks 0, 4, and 8. CRP and FeCal were assessed at BL and through Week 12.

Results: Three hundred thirteen patients were included in the analysis; approximately 50% had a history of inadequate response/intolerance to advanced therapies. Median BL CRP and FeCal concentrations were similar across treatment groups. Greater median reductions in CRP and FeCal were observed at the earliest timepoint assessed (Week 4) with GUS and continued to Week 12 compared with placebo (Table 1). Median changes from BL to Week 12 in CRP were -1.86 mg/L for the combined GUS group compared with 0.06 mg/L for placebo (nominal p< 0.001). Median changes from BL to Week 12 in FeCal were -684.00 mg/kg and 0.00 mg/kg for the combined GUS group and placebo, respectively (nominal p< 0.001). At Week 12, higher proportions of patients treated with GUS compared with placebo had normalized CRP ≤3 mg/L (44.2% vs 18.8%, nominal p< 0.001), and normalized FeCal ≤250 mg/kg (33.0% vs 9.9%, nominal p< 0.001), respectively, among patients with abnormal CRP or FeCal at BL.

Discussion: Patients with moderately to severely active UC who received GUS IV induction treatment had greater reductions in CRP and FeCal concentrations through Week 12 compared with placebo with no dose dependent effect for GUS 200 mg and 400 mg. Reductions in CRP and FeCal were observed as early as Week 4 with GUS and continued to Week 12. Higher proportions of patients had normalized CRP and normalized FeCal levels at Week 12 with GUS compared with placebo.

	Placebo IV (N=105)	Guselkumab 200 mg IV (N=101)	Guselkumab 400 mg IV (N=107)	Guselkumab Combined (N=208)
CRP (mg/L)
Baseline, N Median (IQR)	105 4.89 (1.35; 10.80)	99 4.31 (1.61; 17.80)	104 4.38 (1.88; 8.81)	203 4.37 (1.74; 11.90)
Change from baseline at Week 4, N Median (IQR)	104 0.00 (-1.32, 1.37)	98 -2.18 (-8.60;-0.28)**	101 -1.15 (-5.45; -0.06)**	199 -1.45 (-6.69; -0.17)**
Change from baseline at Week 8, N Median (IQR)	103 0.00 (-2.49; 1.74)	94 -2.60 (-9.30; -0.39)**	102 -1.55 (-4.80; -0.18)**	196 -2.10 (-7.49; -0.23)**
Change from baseline at Week 12, N Median (IQR)	102 0.06 (-2.23; 2.94)	97 -2.31 (-8.20; -0.33)**	100 -1.06 (-4.76; 0.07)**	197 -1.86 (-6.28; -0.06)**
FeCal (mg/kg)
Baseline, N Median (IQR)	91 1457.00 (749.00; 3054.00)	95 1667.00 (771.00; 2859.00)	101 1578.00 (811.00; 2860.00)	196 1619.50 (791.00; 2859.50)
Change from baseline at Week 4, N Median (IQR)	89 -116.00 (-830.00; 812.00)	89 -358.00 (-1641.00; 226.00)	95 -391.00 (-1301.00; 167.00)*	184 -378.00 (-1503.00;207.00)*
Change from baseline at Week 12, N Median (IQR)	77 0.00 (-855.00; 1089.00)	82 -745.00 (-1946.00; 0.00)**	88 -558.50 (-1426.00; -12.50)**	170 -684.00 (-1682.00, -10.00)**
Nominal P< 0.05 *Nominal P< 0.001Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an AE of worsening of UC prior to the designated timepoint had their baseline value carried forward from the time of the event onward. Data after a discontinuation of study agent due to COVID-19 related reasons (excluding COVID 19 infection) were considered to be missing.

Table: Table 1. Change from baseline in CRP and FeCal concentrations through Week 12

Disclosures:

Gary Lichtenstein: Abbvie – Consultant. Allergan – Consultant. American College of Gastroenterology – Honorarium for Associate Editor of American Journal of Gastroenterology. American Gastroenterological Association – CME. American Regent – Consultant, Honorarium (CME Program). Celgene – Consultant, Grant/Research Support. Chemed – CME. Eli Lilly – Consultant, Data Safety Monitoring Board. Endo Pharmaceuticals – Consultant. Ferring – Consultant. Gastroenterology and Hepatology – Gastro-Hep Communication, Editor-Honorarium. Gilead – Consultant. IMEDEX – CME. Ironwood – CME. Janssen/ Janssen Orthobiotech – Consultant, Grant/Research Support, Funding to University of PA (IBD Fellow Education). MedEd Consultants – Consultant. Merck – Consultant, Honorarium (CME Program). Morphic Therapeutics – Consultant. Pfizer Pharmaceuticals – Consultant, Funding to University of PA (IBD Fellow Education). Professional Communications, Inc. – Royalty for writing Textbook. Prometheus Laboratories, Inc – Consultant. Romark – Consultant, Honorarium for CME. Salix Pharmaceuticals/Valeant – Consultant. Sandoz – Consultant. Shire Pharmaceuticals – Consultant. SLACK, Inc – Book Royalty. Springer Science and Business Media – Editor (Honorarium). Takeda – Consultant, Grant/Research Support, Funding to University of PA (IBD Fellow Education). UCB – Consultant, Grant/Research Support. University of Kentucky – CME. Up-To-Date – Author (Honorarium). Vindico – CME. Virgo – Consultant, Stock Options.

Axel Dignass: AbbVie – Consultant, Speakers Bureau. Abivax – Consultant. Amgen – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Celgene/Bristol Myers Squibb – Consultant. Eli Lilly – Consultant, Speakers Bureau. Falk Foundation – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Fresenius Kabi – Consultant. Galapagos – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Pharmacosmos – Consultant. Roche/Genentech – Consultant. Sandoz/Hexal – Consultant. Takeda – Consultant, Speakers Bureau. Tillotts – Consultant, Speakers Bureau. Vifor – Consultant, Speakers Bureau.

William Sandborn: AbbVie – Consultant, Grant/Research Support. Abivax – Consultant. Admirx – Consultant. Alfa sigma – Consultant. Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust) – Consultant. Alivio Therapeutics – Consultant. Allakos – Consultant, Stock Options. Allergan – Consultant. Amgen – Consultant. Applied Molecular Transport – Consultant. Arena Pharmaceuticals – Consultant, Grant/Research Support. Avexegen Therapeutics – Consultant. Aviva – Grant/Research Support. Bausch Health (Salix) – Consultant. BeiGene – Consultant, Stock Options. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant, Grant/Research Support. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant, Grant/Research Support. Celltrion – Consultant. Cellularity – Consultant. Conatus – Consultant. Cosmo Pharmaceuticals – Consultant. Equillium – Consultant. Escalier Biosciences – Consultant. Ferring – Consultant. Forbion – Consultant. Genentech – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant, Grant/Research Support. Glenmark Pharmaceuticals – Consultant. Gossamer Bio – Consultant, Stock Options. GSK – Grant/Research Support. Immunic (Vital Therapies) – Consultant. Incyte – Consultant. Index Pharmaceuticals – Consultant. Intact Therapeutics – Consultant. Janssen – Consultant, Grant/Research Support. Kyowa Kirin Pharmaceutical Research – Consultant. Kyverna Therapeutics – Consultant. Landos Biopharma – Consultant. Lilly – Consultant, Grant/Research Support. Miraca Life Sciences – Consultant. Nivalis Therapeutics – Consultant. Novartis – Consultant. Nutrition Science Partners – Consultant. Oppilan Pharma (acquired by Ventyx Biosciences) – Consultant, Stock Options. Otsuka – Consultant. Pandion Therapeutics – Consultant. Paul Hastings – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant, Stock Options. Prometheus Biosciences – Consultant, Grant/Research Support, Stock Options. Prometheus Laboratories – Consultant, Stock Options. Protagonist Therapeutics – Consultant. Provention Bio – Consultant. Reistone Biopharma – Consultant. Ritter Pharmaceuticals – Consultant. Seres Therapeutics – Consultant, Grant/Research Support. Shanghai Pharma Biotherapeutics – Consultant. Shire – Consultant, Grant/Research Support. Shoreline Biosciences – Consultant, Employee, Stock Options. Sienna Biopharmaceuticals – Consultant. Sigmoid Biotechnologies – Consultant. Sterna Biologicals – Consultant. Sublimity Therapeutics – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. TheraVance Biopharma – Consultant, Grant/Research Support. Thetis Pharmaceuticals – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant. UCB Pharma – Consultant. Vendata Biosciences – Consultant. Ventyx Biosciences – Consultant, Stock Options. Vimalan Biosciences – Consultant, Stock Options. Vivelix Pharmaceuticals – Consultant. Vivreon Biosciences – Consultant, Stock Options. Zealand Pharma – Consultant.

Kuan-Hsiang Huang: Johnson & Johnson – Employee, Stock-publicly held company(excluding mutual/index funds).

Matthew Germinaro: Janssen Research & Development – Employee. Johnson & Johnson – Stock-publicly held company(excluding mutual/index funds).

Rebbecca Wilson: Johnson & Johnson – Employee, Stock-publicly held company(excluding mutual/index funds).

Hongyan Zhang: Johnson & Johnson – Employee, Stock-publicly held company(excluding mutual/index funds).

Baili Chen: Janssen – Grant/Research Support, study investigator.

Minhu Chen: Janssen – Grant/Research Support, study investigator.

Tadakazu Hisamatsu: AbbVie – Consultant, Grant/Research Support, Lecture fees. Celgene – Consultant. Daiichi-Sankyo – Grant/Research Support. EA Pharma Co, Ltd – Consultant, Grant/Research Support, Lecture fees. Janssen Research & Development, LLC – Consultant, lecture fees. JIMRO – Grant/Research Support. JIMRO Co – Consultant, Grant/Research Support. Kyorin Pharmaceutical Co. Ltd – Consultant, Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Grant/Research Support, Lecture fees. Mochida Pharmaceutical Co., Ltd – Grant/Research Support, lecture fees. Nichi-Iko Pharmaceutical Co., Ltd – Consultant. Nippon Kayaku Co., Ltd – Grant/Research Support. Pfizer Inc – Consultant, Grant/Research Support, lecture fees. Takeda Pharmaceutical Co., Ltd – Grant/Research Support, Lecture fees. Zeria Pharmaceutical Co. Ltd – Grant/Research Support.

Brian Feagan: AbbVie – Consultant, Member of the scientific advisory board, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Alimentiv Inc – Employee. Allianthera – Consultant. Amgen – Consultant, Member of the scientific advisory board. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. BioJamp – Consultant. Biopharma – Consultant. Biora Therapeutics – Consultant. Boehringer-Ingelheim – Consultant, Member of scientific advisory board. Boston Pharma – Consultant. Boxer – Consultant. Celgene/BMS – Consultant, Member of scientific advisory board. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 Capital – Consultant, Member of the scientific advisory board. Eli Lilly and Company – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Consultant, Member of scientific advisory board. Gilead – Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, Stock Shareholder. GSK – Consultant, Member of the scientific advisory board. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Consultant, Member of the scientific advisory board. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Consultant, Member of scientific advisory board, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant, Member of the scientific advisory board. Mylan – Consultant. Novartis – Member of the scientific advisory board. OM Pharma – Consultant. Origo BioPharma – Consultant, Member of scientific advisory board. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Consultant, Member of the scientific advisory board. Play to Know AG – Consultant. Progenity – Consultant, Member of the scientific advisory board. Prometheus – Member of scientific advisory board. Prometheus Therapeutics and Diagnostics – Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill – Consultant. REDX – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Consultant, Member of the scientific advisory board, Speakers Bureau. Teva – Consultant, Member of the scientific advisory board. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant, Member of the scientific advisory board. UCB Pharma – Consultant. VHsquared Ltd. – Consultant. Viatris – Consultant. Western University – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

Julian Panés: Abbott – payment for the development of educational presentations, Speakers Bureau. AbbVie – Consultant, Grant/Research Support, support for travel to meetings, during the conduct of the study; payment for development of educational presentations. Arena – Consultant. Athos – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Ferring – Consultant. Galapagos – Consultant. Genentech-Roche – Consultant. GSK – Consultant. Janssen – Consultant, Payment for development of educational presentations, Speakers Bureau. Mirum – Consultant. Morphic – Consultant. MSD – Consultant. Nestlé – Consultant. Origo – Consultant. Pandion – Consultant. Pfizer – Consultant, Grant/Research Support, Payment for development of educational presentations, Speakers Bureau. Progenity – Consultant. Protagonist – Consultant. Revolo – Consultant. Robarts – Consultant. Roche – Payment for development of educational presentations. Takeda – Consultant, Support for travel to meetings during the conduct of the study, Speakers Bureau. Theravance – Consultant, Speakers Bureau. Wassermann – Consultant.

Laurent Peyrin-Biroulet: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Biogaran – Advisory Committee/Board Member, Consultant, Speakers Bureau. Biogen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Forward Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Genentech – Advisory Committee/Board Member, Consultant, Speakers Bureau. H.A.C. Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Hospira/Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Index Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Lycera – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mitsubishi – Advisory Committee/Board Member, Consultant, Speakers Bureau. Norgine – Advisory Committee/Board Member, Consultant, Speakers Bureau. Samsung Bioepis – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant, Speakers Bureau. Tillotts – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vifor – Advisory Committee/Board Member, Consultant, Speakers Bureau.