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Monday Poster Session

Category: IBD

P2157 - Early Disease Clearance With Etrasimod and Correlation With Week 52 Outcomes and Biomarkers: A Post Hoc Analysis of the Phase 3 ELEVATE UC Trials

Monday, October 23, 2023
10:30 AM – 4:15 PM PT
Location: Exhibit Hall
Has Audio
Fernando Magro, MD, PhD1, Laurent Peyrin-Biroulet, MD, PhD2, Bruce E. Sands, MD, MS, FACG3, Silvio Danese, MD, PhD4, Vipul Jairath, MBChB, DPhil5, Martina Goetsch, MD6, Abhishek Bhattacharjee, PhD7, Joseph Wu, PhD8, Diogo Branquinho, MD, MSc9, Irene Modesto, MD, PhD9, Brian G. Feagan, MD5
1University of Porto and Centro Hospitalar São João, São João, Porto, Portugal; 2Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 3Icahn School of Medicine at Mount Sinai, New York, NY; 4IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Lombardia, Italy; 5Western University, London, ON, Canada; 6Pfizer AG, Zurich, Zurich, Switzerland; 7Pfizer Healthcare India Pvt. Ltd, Chennai, Tamil Nadu, India; 8Pfizer Inc., Cambridge, MA; 9Pfizer Inc., New York, NY

Introduction: The concept of disease clearance (DC), which includes symptomatic, endoscopic and histologic remission, has been proposed as the ultimate goal in ulcerative colitis (UC) treatment. However, the prognostic value of this endpoint remains uncertain.1 Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)1,4,5 receptor modulator in development for the treatment of moderately to severely active UC.

Methods: We report a post hoc analysis from the ELEVATE UC trials to assess relationships between histological/composite endpoints, biomarkers and efficacy outcomes in etrasimod-treated patients (pts). In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts with moderately to severely active UC were randomized 2:1 to once‑daily etrasimod 2 mg or placebo (PBO). DC was defined as Nancy Histological Index=0, Mayo endoscopic subscore (ES)=0, rectal bleeding subscore=0, stool frequency subscore=0 or 1 (if 1, must have ≥ 1 point decrease from baseline). Other endpoints are defined in the Table. Kappa correlation coefficients2 were estimated between histological endpoints at Wk 12 and efficacy outcomes at Wk 52, and between histological endpoints and biomarkers at Wks 12 and 52.

Results: At Wk 12 in both trials, DC was achieved by more etrasimod- than PBO-treated pts (8.4% [23/274] vs 1.5% [2/135] and 9.9% [22/222] vs 4.5% [5/112], p < 0.001 and p=0.042, respectively). The proportion of pts with clinical remission at Wk 52 was higher among pts who achieved DC at Wk 12 (17/23; 74%) vs pts who did not (71/251; 28%). Histologic-endoscopic mucosal improvement at Wk 12 had the highest correlation with efficacy outcomes at Wk 52 (κ 0.357–0.438; Table). Fecal calprotectin and C‑reactive protein normalization showed slight/fair to substantial agreement with histologic endpoints (κ 0.223–0.630; 0.075–0.6, respectively; Table). Absolute lymphocyte count < 0.5x109/L showed no agreement (κ -0.100–0.216; Table).

Discussion: Early achievement of DC showed only fair correlation with Wk 52 efficacy outcomes. Correlation of fecal calprotectin < 150 mg/kg with histological endpoints was most often moderate and improved from Wks 12 to 52. A different approach is needed for development of robust predictive models.

References


1. D’Amico F et al. United Eur Gastroenterol J 2022; 10: 777–784.

2. Cohen JA et al. Educ Psychol Meas 1960; 20: 37–46.








Disclosures:
Fernando Magro: AbbVie – Personal fees. Amgen – personal fees. Biogen – Personal fees. Celgene – Personal fees. Celltrion – Personal fees. Dr. Falk Pharma – Personal fees. Ferring – Personal fees. GEDII – Grant/Research Support. Hospira – Personal fees. Janssen – Personal fees. Laboratórios Vitória – Personal fees. MSD – Personal fees. National Science Foundation – Grant/Research Support. Pfizer Inc – Personal fees. Sandoz – Personal fees. Takeda – Personal fees. UCB – Personal fees. Vifor – Personal fees.
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.
Vipul Jairath: AbbVie – Advisory Committee/Board Member, consulting/advisory board fees, speaker’s fees. Alimentiv Inc – consulting/advisory board fees. Arena pharmaceuticals – consulting/advisory board fees. Asahi Kasei Pharma – consulting/advisory board fees. Asieris – consulting/advisory board fees. Astra Zeneca – consulting/advisory board fees. Bristol Myers Squibb – consulting/advisory board fees, speaker’s fees. Celltrion – consulting/advisory board fees. Eli Lilly and Company – consulting/advisory board fees. Ferring – consulting/advisory board fees, speaker’s fees. Flagship Pioneering – consulting/advisory board fees. Fresenius Kabi – consulting/advisory board fees, speaker’s fees. Galapagos – consulting/advisory board fees, speaker’s fees. Genentech – consulting/advisory board fees. Gilead – consulting/advisory board fees. GlaxoSmithKline – consulting/advisory board fees. Janssen – consulting/advisory board fees, speaker’s fees. Merck – consulting/advisory board fees. Metacrine – consulting/advisory board fees. Mylan – consulting/advisory board fees. Pandion – consulting/advisory board fees. Pendopharm – consulting/advisory board fees. Pfizer – consulting/advisory board fees, speaker’s fees. Prometheus – consulting/advisory board fees. Protagonist – consulting/advisory board fees. Reistone Biopharma – consulting/advisory board fees. Roche – consulting/advisory board fees. Sandoz – consulting/advisory board fees. Second Genome – consulting/advisory board fees. Shire – speaker’s fees. Sorriso pharmaceuticals – consulting/advisory board fees. Takeda – consulting/advisory board fees, speaker’s fees. Teva – consulting/advisory board fees. Topivert – consulting/advisory board fees. Ventyx – consulting/advisory board fees. Vividion – consulting/advisory board fees.
Martina Goetsch: Pfizer AG – Employee. Pfizer Inc – Stock-publicly held company(excluding mutual/index funds).
Abhishek Bhattacharjee: Pfizer Healthcare India – Employee. Pfizer Inc – Stock Options.
Joseph Wu: Pfizer Inc – Employee, Stock Options.
Diogo Branquinho: Pfizer Inc – Employee, Stock Options.
Irene Modesto: Pfizer Inc – Employee, Stock Options.
Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. Baxter – Consultant. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boston Pharma – Consultant. Bristol Myers Squibb – Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring Pharmaceuticals – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, stock shareholder. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, 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 – Advisory Committee/Board Member, Consultant. Mylan – Consultant. Novartis – Advisory Committee/Board Member. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Therapeutics and Diagnostics – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill Biopharma – Consultant. Redx – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. UCB Pharma – Consultant. VHSquared Ltd. – Consultant. Viatris – Consultant. Western University, Alimentiv Inc – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.


Fernando Magro, MD, PhD1, Laurent Peyrin-Biroulet, MD, PhD2, Bruce E. Sands, MD, MS, FACG3, Silvio Danese, MD, PhD4, Vipul Jairath, MBChB, DPhil5, Martina Goetsch, MD6, Abhishek Bhattacharjee, PhD7, Joseph Wu, PhD8, Diogo Branquinho, MD, MSc9, Irene Modesto, MD, PhD9, Brian G. Feagan, MD5. P2157 - Early Disease Clearance With Etrasimod and Correlation With Week 52 Outcomes and Biomarkers: A Post Hoc Analysis of the Phase 3 ELEVATE UC Trials, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.