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Oral Paper Presentation

Annual Scientific Meeting

Session: Plenary Session 2B - Small Intestine / IBD

35 - Risankizumab Induction Therapy in Patients WIth Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomized Phase 3 INSPIRE Study

Tuesday, October 24, 2023
9:40 AM – 9:50 AM PT
Location: Ballroom B
Livestream
Edouard Louis, MD1, Remo Panaccione, MD2, Gareth Parkes, MD3, Laurent Peyrin-Biroulet, MD4, Marc Ferrante, MD5, Ken Takeuchi, MD, PhD6, Britta Siegmund, MD, PhD7, Phillip Levine, MD8, Jasmina Kalabic, MD9, Ezequiel Neimark, MD8, Kori Wallace, MD8, Su Chen, PhD8, W.Rachel Duan, MD8, Alessandro Armuzzi, MD10, Luc Biedermann, MD11, Edward V. Loftus, MD12, Gil Melmed, MD, MS13, Stefan Schreiber, MD14
1University Hospital CHU of Liège, Liege, Liege, Belgium; 2University of Calgary, Calgary, AB, Canada; 3Barts Health NHS Trust, London, England, United Kingdom; 4Lorraine University, Vandoeuvre, Lorraine, France; 5University Hospitals Leuven, Leuven, Liege, Belgium; 6Tsujinaka Hospital Kashiwanoha, Kashiwa, Chiba, Japan; 7Charité – Universitätsmedizin Berlin, Berlin, Berlin, Germany; 8AbbVie, North Chicago, IL; 9AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Baden-Wurttemberg, Germany; 10IRCCS Humanitas Research Hospital, Milan, Abruzzi, Italy; 11University Hospital Zürich, Zürich, Zurich, Switzerland; 12Mayo Clinic College of Medicine and Science, Rochester, MN; 13Center for Inflammatory Bowel Diseases, Cedars-Sinai Medical Center, Los Angeles, CA; 14University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

Introduction: Risankizumab (RZB), a monoclonal antibody neutralizing interleukin (IL)-23p19, was evaluated for efficacy and safety of induction therapy in patients with moderately to severely active ulcerative colitis (UC) in a large phase 3 trial, INSPIRE (NCT03398148).

Methods: Eligible patients (18-80 years) with moderately to severely active UC (Adapted Mayo score of 5–9 points) and an endoscopic subscore of 2-3 (per central review) were enrolled. Patients were required to have a diagnosis of UC for at least 3 months prior to baseline, and demonstrated intolerance or inadequate response to conventional and/or advanced therapies (biologics, JAK inhibitors, and S1P receptor modulators). Patients (N=975) were randomized 2:1 to receive either RZB 1200 mg intravenously (IV) or placebo (PBO) at Weeks (Wks) 0, 4, and 8. The primary endpoint was clinical remission (per Adapted Mayo score) at Wk 12 (see Figure legend for definitions). Key, ranked secondary endpoints included clinical response, endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI), and histologic-endoscopic mucosal remission (HEMR), which were measured at Wk 12, unless otherwise noted.

Results: Baseline characteristics were similar between treatment groups. Significantly more patients receiving RZB achieved clinical remission vs PBO (20.3% vs 6.2%, adjusted treatment difference 14.0% [95% CI, 10.0%-18.0%], P< .00001, Figure 1A). All ranked secondary endpoints were met. RZB attained higher rates of clinical response (per Adapted Mayo score at Wk 12 and per Partial Adapted Mayo score at Wk 4), endoscopic improvement, endoscopic remission, HEMI, and HEMR, compared to PBO (P< .00001 for all endpoints, Figure 1B). Adverse event (AE) rates were 42.1% in RZB vs 49.7% PBO, serious AEs (2.3% vs 10.2%), severe AEs (2.5% vs 10.2%), AEs leading to discontinuation of study drug (0.6% vs 3.7%), and serious infections (0.6% vs 1.2%) were numerically lower in the RZB arm. No adjudicated major adverse cardiovascular events, adjudicated anaphylaxis, or serious hepatic events were reported. One death occurred in the RZB group due to COVID-19 pneumonia.

Discussion: In patients with moderately to severely active UC, RZB was superior to PBO as an induction therapy for clinical remission and all secondary clinical, endoscopic, and endoscopic-histologic endpoints. RZB was well-tolerated, and no new safety risks were observed.

Figure: Figure 1. Primary and Key Secondary Endpoints
All patients in this dataset were included here within the ITT population. Endpoints were assessed at Week 12 unless otherwise noted.
Clinical Remission per Adapted Mayo score: Stool frequency subscore ≤ 1 and not greater than baseline, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1 without friability
Clinical Response per Adapted Mayo: Decrease from baseline ≥ 2 points and ≥ 30%, in addition to a decrease in RBS ≥ 1 or an absolute rectal bleeding score (RBS) ≤ 1
Clinical Response per Partial Adapted Mayo: Decrease from baseline ≥ 1 point and ≥ 30% a decrease in RBS ≥ 1 or an absolute RBS ≤ 1
Endoscopic Improvement: Endoscopic subscore of 0 or 1 without friability
Endoscopic Remission: Endoscopic subscore = 0
Histologic-Endoscopic Mucosal Improvement (HEMI): Endoscopic subscore of 0 or 1 without friability and Geboes score ≤ 3.1
Histologic-Endoscopic Mucosal Remission (HEMR): Endoscopic subscore of 0 and Geboes score < 2.0
Results were stratified by baseline corticosteroid use (yes vs no), baseline Adapted Mayo score (≤ 7 vs > 7), and the number of advanced therapy failures (0, 1, >1). Results are based on non-responder imputation incorporating multiple imputation (NRI-MI) to handle missing data due to COVID-19 or due to geopolitical conflict in Ukraine or surrounding areas. ***P-value <.00001 vs PBO. P-value for treatment difference between RZB 1200 mg IV and PBO, using Cochran-Mantel­Haenszel (CMH) test for categorical endpoints, controlling for stratification factors. IR, inadequate response


Disclosures:
Edouard Louis: AbbVie – Advisory Committee/Board Member, Consultant, educational grants, Speakers Bureau. Arena – Advisory Committee/Board Member. Celgene – Advisory Committee/Board Member. Falk – Speakers Bureau. Ferring – Advisory Committee/Board Member, Speakers Bureau. Galapagos – Advisory Committee/Board Member. Gilead – Advisory Committee/Board Member. Hospira – Advisory Committee/Board Member, Speakers Bureau. Janseen – Advisory Committee/Board Member, Grant/Research Support, educational grants. MSD – Advisory Committee/Board Member, educational grants, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Grant/Research Support, educational grants, Speakers Bureau. Takeda – Advisory Committee/Board Member, Grant/Research Support, educational grants.
Remo Panaccione: Abbott – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Alimentiv (formerly Robarts), – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Amgen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Arena Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. AstraZeneca – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Celgene – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Cosmos Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Eisai – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Elan – Advisory Committee/Board Member, Consultant, Grant/Research Support, Stock Options. Elii Lilly – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Ferring – Advisory Committee/Board Member, Consultant, Grant/Research Support, Stock Options. Galapagos – Consultant, Grant/Research Support, Speakers Bureau, Stock Options. Genetech – Consultant, Grant/Research Support, Speakers Bureau, Stock Options. Gilead Sciences – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. GlaxoSmithKline – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Janseen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Mylan – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Oppilan Pharma – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Pandion Pharma – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Progenity – Advisory Committee/Board Member, Consultant, Grant/Research Support, Stock Options. Protagonist Therapeutics – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Roche – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Satisfai Health – Advisory Committee/Board Member, Consultant, Grant/Research Support, Stock Options. Schering-Plough – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Shire – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Sublimity Therapeutics – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Takeda Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Theravance Biopharma – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. UCB – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau.
Gareth Parkes: AbbVie – Consultant, Grant/Research Support. Allergan – Consultant. Ampersand Health – Stock-privately held company. BMS – Consultant. Celltrion – Consultant. Ferring – Consultant. Galapagos – Consultant. Janseen – Consultant. Napp Pharmaceuticals – Consultant. Pfizer – Consultant. Sorriso Pharmaceuticals – Consultant. Takeda – Consultant, Grant/Research Support. Tillotts – Consultant.
Laurent Peyrin-Biroulet: AbbVie – Consultant, Speakers Bureau. Abivax – Consultant. Alimentiv (formerly Robarts), – Consultant. Alma Bio Therapeutics – Consultant. Amgen – Consultant, Speakers Bureau. Applied Molecular Transport – Consultant. Arena – Consultant, Speakers Bureau. Biogen – Consultant, Speakers Bureau. BMS – Consultant. Celltrion – Consultant, Grant/Research Support, Speakers Bureau. CONNECT Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, Speakers Bureau. Enthera – Consultant. Ferring – Consultant, Speakers Bureau. Fresenius Kabi – Consultant, Grant/Research Support. Galapagos – Consultant, Speakers Bureau. Genentech – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Gossamer Bio – Consultant. GSK – Consultant. HAC-Pharma – Consultant. IAG Image Analysis – Consultant. Index Pharmaceuticals – Consultant. Inoterm – Consultant. Janseen – Consultant, Speakers Bureau. Medac – Consultant, Speakers Bureau. Mopac – Consultant. Morphic – Consultant. MSD – Consultant, Speakers Bureau. Norgine – Consultant. Novartis – Consultant. OM Pharma – Consultant. ONO Pharma – Consultant. OSE Immunotherapeutics – Consultant. Pandion Therapeutics – Consultant. Par'Immune – Consultant. Pfizer – Consultant, Speakers Bureau. Prometheus – Consultant. Protagonist – Consultant. Roche – Consultant. Roivant – Consultant. Samsung – Consultant. Sandoz – Consultant, Speakers Bureau. Sanofi – Consultant. Takeda – Consultant, Grant/Research Support, Speakers Bureau. Theravance – Consultant. Thermo Fisher – Consultant. Tigenix – Consultant. Tillotts – Consultant, Speakers Bureau. Vectivbio – Consultant. Ventyx – Consultant. Viatris – Consultant, Speakers Bureau. Vifor – Consultant. Ysopia – Consultant.
Marc Ferrante: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Agomab Therapeutics – Consultant. Amgen – Grant/Research Support, Speaker's fees. Bioepis – Consultant. Biogen – Grant/Research Support, Speaker's fees. Boehringer Ingelheim – Consultant, Speaker's fees. Celgene – Consultant. Celltrion – Consultant. EG – Grant/Research Support. Eli Lilly – Consultant. Falk – Consultant. Ferring – Consultant. Janseen – Grant/Research Support. Janssen-Cilag – Consultant, Speaker's fees. Lamepro – Consultant. Medtronic – Consultant. MSD – Consultant, Speaker's fees. Pfizer – Consultant, Grant/Research Support, Speaker's fees. Regeneron – Consultant. Regeneron – Consultant. Samsung – Consultant. Sandoz – Consultant, Speaker's fees. Takeda – Consultant, Grant/Research Support, Speaker's fees. ThermoFisher – Consultant. Truvion Healthcare – Speaker's fees. Viatris – Grant/Research Support, Speaker's fees.
Ken Takeuchi: AbbVie – Grant/Research Support, Speakers Bureau. Celltrion – Speakers Bureau. EA pharma – Speakers Bureau. Janssen – Speakers Bureau. Kyorin – Speakers Bureau. Mochida – Speakers Bureau. Takeda – Grant/Research Support, Speakers Bureau. Tanabe Mitsubishi – Speakers Bureau. Thermo Fisher Diagnostics K.K. – Consultant. Zeria – Speakers Bureau.
Britta Siegmund: Abbvie – Consultant, Speakers Bureau. Arena – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. CED Service GmbH – Speakers Bureau. Celgene – Consultant. Eli Lilly – Consultant. Endpoint Health – Consultant. Falk Pharma – Consultant, Speakers Bureau. Ferring – Speakers Bureau. Galapagos – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. PredictImmune – Consultant. Prometheus – Consultant. Takeda – Consultant, Speakers Bureau.
Phillip Levine: AbbVIe – Employee, Stock Options.
Jasmina Kalabic: AbbVie – Employee, Stock Options.
Ezequiel Neimark: AbbVIe – Employee, Stock Options.
Kori Wallace: AbbVie – Employee, Stock Options.
Su Chen: AbbVie – Employee, Stock Options.
W.Rachel Duan: AbbVie – Employee, Stock Options.
Alessandro Armuzzi: AbbVie – Consultant, Speaker's fees. Allergan – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant, Speaker's fees. Arena – Advisory Committee/Board Member, Consultant. Biogen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's fees. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speaker's fees. Celltrion – Advisory Committee/Board Member, Consultant, Speaker's fees. Eli Lilly – Advisory Committee/Board Member, Consultant, Speaker's fees. Ferring – Advisory Committee/Board Member, Consultant, Speaker's fees. Galapagos – Advisory Committee/Board Member, Consultant, Speaker's fees. Gilead – Advisory Committee/Board Member, Consultant, Speaker's fees. Janssen – Advisory Committee/Board Member, Consultant, Speaker's fees. Mitsubishi Tanabe – Speaker's fees. MSD – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's fees. Mylan – Advisory Committee/Board Member, Consultant. Novartis – Speaker's fees. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's fees. Protagonist Therapeutics – Advisory Committee/Board Member, Consultant. Roche – Advisory Committee/Board Member, Consultant, Speaker's fees. Samsung Bioepis – Advisory Committee/Board Member, Consultant, Speaker's fees. Sandoz – Advisory Committee/Board Member, Consultant, Speaker's fees. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's fees. Tigenix – Speaker's fees.
Luc Biedermann: AbbVie – Advisory Committee/Board Member, Consultant, Speaker's fees. Amgen – Advisory Committee/Board Member. BMS – Advisory Committee/Board Member, Consultant, Speaker's fees. Falk – Advisory Committee/Board Member, Consultant, Speaker's fees. Janseen – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member, Consultant, Speaker's fees. Sanofi – Advisory Committee/Board Member, Consultant, Speaker's fees. Takeda – Advisory Committee/Board Member, Consultant, Speaker's fees.
Edward Loftus: AbbVie – Consultant, Grant/Research Support. Alvotech – Consultant. Amgen – Consultant. Arena – Consultant. Avalo Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support. Celgene – Consultant, Grant/Research Support. Celltrion – Consultant. Exact Sciences – Stock-publicly held company(excluding mutual/index funds). Fresenius Kabi – Consultant. Genentech – Consultant, Grant/Research Support. Gilead – Consultant, Grant/Research Support. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant, Grant/Research Support. Iota Biosciences – Consultant. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. KSL Diagnostics – Consultant. Lilly – Consultant. Morphic – Consultant. Ono Pharma – Consultant. Pfizer – Consultant, Grant/Research Support. Protagonist – Consultant. Receptos – Grant/Research Support. Robarts Clinical Trials – Grant/Research Support. Scipher Medicine – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. Theravance – Grant/Research Support. UCB – Consultant, Grant/Research Support.
Gil Melmed: AbbVie – Consultant. Amgen – Consultant. Arena – Consultant. BI – Consultant. BMS – Consultant. Dieta – Consultant, Owner/Ownership Interest. Eli Lilly – Employee. Ferring – Consultant. Fresenius Kabi – Consultant. Genetech – Consultant. Gilead – Consultant. Janseen – Consultant. Oshi – Consultant, Owner/Ownership Interest. Pfizer – Consultant, Grant/Research Support. Prometheus Labs – Consultant. Samsung Bioepis – Consultant. Takeda – Consultant. Techlab – Consultant. Viatris – Consultant.
Stefan Schreiber: AbbVie – Personal fees. Amgen – Personal fees. Arena Pharmaceuticals – Personal fees. Biogen – Personal fees. Bristol Myers Squibb – Personal fees. Celgene – Personal fees. Celltrion Healthcare – Personal fees. Dr. Falk Pharma – Personal fees. Eli Lilly – personal fees. Ferring Pharmaceuticals – personal fees. Fresenius Kabi – Personal fees. Galapagos – Personal fees. Gilead – Personal fees. Hikma Pharmaceuticals – Personal fees. I-Mab – Personal fees. Janssen Pharmaceuticals – Personal fees. Morphic – Personal fees. MSD – Personal fees. Mylan – Personal fees. Pfizer – Personal fees. Protagonist – Personal fees. ProventionBio – Personal fees. Sandoz/Hexal – personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. UCB – personal fees.


Edouard Louis, MD1, Remo Panaccione, MD2, Gareth Parkes, MD3, Laurent Peyrin-Biroulet, MD4, Marc Ferrante, MD5, Ken Takeuchi, MD, PhD6, Britta Siegmund, MD, PhD7, Phillip Levine, MD8, Jasmina Kalabic, MD9, Ezequiel Neimark, MD8, Kori Wallace, MD8, Su Chen, PhD8, W.Rachel Duan, MD8, Alessandro Armuzzi, MD10, Luc Biedermann, MD11, Edward V. Loftus, MD12, Gil Melmed, MD, MS13, Stefan Schreiber, MD14, 35, Risankizumab Induction Therapy in Patients WIth Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomized Phase 3 INSPIRE Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.