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Tuesday Poster Session

Category: IBD

P3600 - PRA023 Improved Bowel Urgency, Nocturnal Bowel Movement, Nocturnal Waking, and Abdominal Pain in a Phase 2 Trial of Patients with Moderately to Severely Active Ulcerative Colitis

Tuesday, October 24, 2023
10:30 AM – 4:00 PM PT
Location: Exhibit Hall
Has Audio
Marla C. Dubinsky, MD1, David T. Rubin, MD2, Laurent Peyrin-Biroulet, MD, PhD3, Bruce E. Sands, MD, MS, FACG4, Silvio Danese, MD, PhD5, Gil Melmed, MD, MS6, Brigid S.. Boland, MD7, Deanna D.. Nguyen, MD8, Quinn Dinh, MD8, JD Lu, PhD8, Bin Dong, 8, Christopher Ma, MD9, Timothy E.. Ritter, MD10, Remo Panaccione, MD11
1Mount Sinai Kravis Children’s Hospital, New York, NY; 2Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL; 3Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Lombardia, Italy; 6Center for Inflammatory Bowel Diseases, Cedars-Sinai Medical Center, Los Angeles, CA; 7University of California, San Diego, CA; 8Prometheus Biosciences, Inc., San Diego, CA; 9Alimentiv Inc., University of Calgary, London, ON, Canada; 10GI Alliance, Southlake, TX; 11University of Calgary, Calgary, AB, Canada

Introduction: PRA023 is an anti–tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for treating inflammatory bowel diseases. In Cohort 1 of a phase 2, double-blind, placebo-controlled trial (ARTEMIS-UC) that enrolled patients with moderately to severely active ulcerative colitis (UC), PRA023 achieved the primary endpoint of clinical remission and all ranked secondary endpoints for this cohort after 12 weeks of induction therapy. In a post hoc analysis, we assessed the impact of PRA023 on UC-associated health-related symptoms, including bowel urgency, nocturnal bowel movements (BM), and abdominal pain.

Methods: Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore ≥2, rectal bleeding subscore ≥1, and history of corticosteroid dependence or insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies were randomized 1:1 to placebo or intravenous PRA023 (1000 mg on day 1, and 500 mg at weeks 2, 6, and 10). Patients recorded nocturnal BM and bowel urgency daily with an electronic diary. Bowel urgency during the prior 24 hours was measured using the Urgency Numeric Rating Scale (UNRS 0 [no urgency] to 10 [worst possible urgency]). For patients with baseline UNRS ≥3, clinically meaningful improvement (CMI) was defined as ≥3-point decrease, and bowel urgency remission was defined as a score of ≤1, where nonresponder imputation was applied to the missing data. Nocturnal waking and abdominal pain were reported via the Inflammatory Bowel Disease Questionnaire at baseline and week 12.

Results: Of 127 patients with baseline UNRS ≥3, a significantly greater proportion of patients receiving PRA023 achieved CMI in bowel urgency (52.4% PRA023 vs 20.3% placebo, ∆32.1%, p=0.0002) and bowel urgency remission (22.2% PRA023 vs 3.1% placebo, ∆19.1%, p=0.0013) at week 12. A significant decrease in bowel urgency and nocturnal BM was observed as early as week 2 and was improved further throughout the 12-week induction period (Figure 1). Nocturnal waking and abdominal pain were significantly improved in patients treated with PRA023 compared to placebo. The least-squares mean (SE) change in rating scale from baseline to week 12 in PRA023 treated patients compared to placebo was 1.74 (0.21) vs 0.87 (0.22) for nocturnal waking and 1.62 (0.17) vs 0.93 (0.18) for abdominal pain.

Discussion: In patients with moderately to severely active UC, PRA023 significantly decreased bowel urgency, nocturnal BM, nocturnal waking, and abdominal pain.

Figure: Figure 1. Change from Baseline in Bowel Urgency (A) and Nocturnal Bowel Movements (B) Over 12 Weeks of Treatment with PRA023

Data are least squares mean ± SE change from baseline in response to the following daily diary questions: (A) On a scale of 0 to 10, have you experienced any urgency with your bowel movements? or (B) Of the bowel movements over the last 24 hours, how many required your waking up from sleep?
**p<0.01; ***p<0.001.


Disclosures:
Marla Dubinsky: AbbVie – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Astra Zeneca – Consultant. Celgene – Consultant. Genentech Inc. – Consultant. Gilead Sciences – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Consultant. Pfizer – Consultant, Grant/Research Support. Prometheus Biosciences – Consultant, Grant/Research Support. Prometheus Labs – Consultant, Grant/Research Support. Takeda – Consultant, Licensing fees. Thabor – Consultant. Trellus Health – Stock-publicly held company(excluding mutual/index funds). UCB Pharma – Consultant.
David Rubin: AbbVie – Consultant, personal fees. AltruBio – Consultant, personal fees. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant, personal fees. Bristol Myers Squibb – Consultant. Celgene Chronicles – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Corp/Syneos – Consultant. Eco R1 – Consultant. GastroIntestinal Research Foundation – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant, personal fees. Helmsley Charitable Trust – Grant/Research Support. Iterative Health – Consultant. Janssen Pharmaceuticals – Consultant, personal fees. Kaleido Biosciences – Consultant. Lilly – Consultant. Pfizer – Consultant, personal fees. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant, personal fees. Seres Therapeutics – Consultant. Takeda – Consultant, Grant/Research Support, Personal fees. Target RWE – Consultant. Trellus Health – Consultant.
Laurent Peyrin-Biroulet: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Allergan – personal fees. Alma – personal fees. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Applied Molecular Transport – personal fees. Arena – personal fees. 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. Bristol Myers Squibb – personal fees. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. CTMA – Stock Options. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Enterome – personal fees. Enthera – personal fees. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Forward Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Fresenius – personal fees. Genentech – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead – personal fees. H.A.C. Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Hikma – personal fees. 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. MSD – Grant/Research Support, personal fees. Mylan – personal fees. Nestlé – personal fees. Norgine – Advisory Committee/Board Member, Consultant, Speakers Bureau. Oppilan Pharma – personal fees. OSE Immunotherapeutics – personal fees. Pfizer – personal fees. Pharmacosmos – personal fees. Roche – personal fees. Samsung Bioepis – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sterna – personal fees. Sublimity Therapeutics – personal fees. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant, Speakers Bureau. Tillots – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vifor – Advisory Committee/Board Member, Consultant, Speakers Bureau.
Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.
Silvio Danese: AbbVie – Consultant, personal fees (lecture fees). Alimentiv – Consultant. Allergan – Consultant, personal fees. Amgen – Consultant, lecture fees. Applied Molecular Transport – Consultant. AstraZeneca – Consultant, personal fees. Athos Therapeutics – Consultant, personal fees. Biogen – Consultant, personal fees. Boehringer Ingelheim – Consultant, personal fees. Bristol Myers Squibb – Consultant. Celgene – Consultant, personal fees. Celltrion Healthcare – Consultant, Personal fees. Dr Falk Pharma – Consultant. Eli Lilly – Consultant, personal fees. Enthera – Consultant, personal fees. Ferring Pharmaceuticals – Consultant, lecture fees. Gilead – Consultant, lecture fees. Hospira – Consultant, personal fees. Inotrem – Consultant, personal fees. Janssen Pharmaceuticals – Consultant, lecture fees. Johnson & Johnson – Consultant, personal fees. Morphic – Consultant. MSD – Consultant, personal fees. Mundipharma – Consultant, personal fees. Mylan – Consultant, lecture fees. Pfizer – Consultant, lecture fees. Roche – Consultant, personal fees. Sandoz – Consultant, personal fees. Sublimity Therapeutics – Consultant, personal fees. Takeda – Consultant, lecture fees. Teladoc Health – Consultant. TiGenix – Consultant, personal fees. UCB – Consultant, personal fees. Vial – Consultant. Vifor – Consultant, personal fees.
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.
Brigid Boland: Bristol Myer Squibb – Advisory Committee/Board Member. Gilead – Grant/Research Support. Pfizer – Advisory Committee/Board Member. Prometheus Biosciences – Grant/Research Support.
Deanna Nguyen: Prometheus Biosciences – Employee.
Quinn Dinh: Prometheus Biosciences – Employee, Stock-publicly held company(excluding mutual/index funds).
JD Lu: Prometheus Biosciences – Employee.
Bin Dong: Prometheus Biosciences – Employee.
Christopher Ma: AbbVie – Consultant, Speakers Bureau. Alimentiv – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. AVIR Pharma Inc – Consultant, Speakers Bureau. BioJAMP – Consultant. Bristol Myers Squibb – Consultant, Speakers Bureau. Celltrion – Consultant. Ferring – Consultant, Grant/Research Support, Speakers Bureau. Fresenius Kabi – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. McKesson – Consultant. Mylan – Consultant. Pendopharm – Consultant, Speakers Bureau. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. Prometheus Biosciences Inc. – Consultant. Roche – Consultant. Sanofi – Consultant. Springer Publishing – Royalties. Takeda – Consultant, Speakers Bureau.
Timothy Ritter: Abbvie – Advisory Committee/Board Member, Speakers Bureau. ArdelyxArena – Advisory Committee/Board Member. Boehringer Ingelheim – Advisory Committee/Board Member. Bristol-Myers Squibb – Advisory Committee/Board Member, Speakers Bureau. Celgene – Advisory Committee/Board Member. Ferring – Advisory Committee/Board Member. Genentech/Roche Gilead – Advisory Committee/Board Member. Intercept – Advisory Committee/Board Member. Iterative Scopes – Advisory Committee/Board Member, Stock-publicly held company(excluding mutual/index funds). Janssen – Advisory Committee/Board Member, Speakers Bureau. Lilly – Advisory Committee/Board Member. Pfizer inc – Advisory Committee/Board Member, Speakers Bureau. Prometheus Biosciences – Advisory Committee/Board Member. Sanofi – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Speakers Bureau.
Remo Panaccione: Abbivax – Consultant. Abbott – Consultant. AbbVie – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena – Consultant. AstraZeneca – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Celltrion – Consultant. Cosmos Technology – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. JAMP Bio – Consultant. Janssen – Consultant. Merck – Consultant. Mylan – Consultant. Novartis – Consultant. Oppilan Pharma – Consultant. Organon – Consultant. Pandion Pharma – Consultant. Pendopharm – Consultant. Pfizer Inc – Consultant. Progenity – Consultant. Prometheus – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant. Sandoz – Consultant. Satisfai Health – Consultant. Shire – Consultant. Sublimity Therapeutics – Consultant. Takeda Pharmaceuticals – Consultant. Theravance Biopharma – Consultant. Trellus – Consultant. UCB – Consultant. Ventyx – Consultant. Viatris – Consultant.


Marla C. Dubinsky, MD1, David T. Rubin, MD2, Laurent Peyrin-Biroulet, MD, PhD3, Bruce E. Sands, MD, MS, FACG4, Silvio Danese, MD, PhD5, Gil Melmed, MD, MS6, Brigid S.. Boland, MD7, Deanna D.. Nguyen, MD8, Quinn Dinh, MD8, JD Lu, PhD8, Bin Dong, 8, Christopher Ma, MD9, Timothy E.. Ritter, MD10, Remo Panaccione, MD11. P3600 - PRA023 Improved Bowel Urgency, Nocturnal Bowel Movement, Nocturnal Waking, and Abdominal Pain in a Phase 2 Trial of Patients with Moderately to Severely Active Ulcerative Colitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.