P0729 - Efficacy and Durability of Ozanimod by Baseline Endoscopic Disease Activity in Advanced Therapy–Naive Ulcerative Colitis Patients Suboptimally Controlled on Conventional Therapies

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Presenting Author(s)

David Rubin, MD, FACG (he/him/his)

University of Chicago Medicine, Inflammatory Bowel Disease Center
Chicago, IL

Award: Presidential Poster Award

David T. Rubin, MD, FACG¹, Britta Siegmund, MD, PhD², Geert R. D’Haens, PhD³, Peter M.. Irving, MD⁴, Irina Blumenstein, MD, PhD⁵, Corey A. Siegel, MD, MS⁶, Edward V.. Loftus, MD⁷, Douglas C. Wolf, MD, FACG⁸, Bincy Abraham, MD, MS, FACG⁹, Freddy Caldera, DO, MS¹⁰, Laurent Peyrin-Biroulet, MD, PhD¹¹, Anjali Jain, PhD¹², Hsiuanlin Wu, MS¹², Mark T. Osterman, MD, PhD¹², Millie D. Long, MD, MPH¹³
¹University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL; ²Charité – Universitätsmedizin Berlin, Berlin, Berlin, Germany; ³Amsterdam University Medical Center, Amsterdam, Drenthe, Netherlands; ⁴Guy’s and St. Thomas’ NHS Foundation Trust, London, England, United Kingdom; ⁵Goethe University Hospital, Frankfurt, Brandenburg, Germany; ⁶Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; ⁷Mayo Clinic College of Medicine and Science, Rochester, MN; ⁸Center for Crohn’s Disease & Ulcerative Colitis, Atlanta Gastroenterology Associates, Atlanta, GA; ⁹Houston Methodist-Weill Cornell, Houston, TX; ¹⁰University of Wisconsin School of Medicine and Public Health, Madison, WI; ¹¹Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; ¹²Bristol Myers Squibb, Princeton, NJ; ¹³UNC Chapel Hill, Chapel Hill, NC

Introduction: Many patients (pts) with ulcerative colitis (UC) initiate conventional therapies (CTs; 5-aminosalicylate, corticosteroids, and thiopurines) but are hesitant to progress to biologic advanced therapies (ATs). Ozanimod (OZA), an oral small molecule AT, is approved in multiple countries for the treatment of moderately to severely active UC.

Methods: This analysis of the phase 3 True North (TN) study and subsequent open-label extension (OLE) explored OZA efficacy and durability in AT-naive UC pts inadequately controlled on CTs at TN baseline. AT-naive pts were grouped by baseline endoscopic disease activity as moderate (Mayo endoscopy subscore [MES]=2) or severe (MES=3). In the 10-wk induction period (IP), pts in Cohort 1 (C1) were randomized to OZA 0.92 mg or placebo (PBO) or received open-label OZA in Cohort 2. OZA clinical responders at Week (W) 10 were rerandomized to OZA (OZA/OZA) or PBO (OZA/PBO) during the maintenance period (MP) through W52. W52 OZA/OZA clinical responders continued in the OLE. Clinical and mucosal efficacy endpoints were evaluated at IP W10, MP W52, OLE W46, and OLE W94.

Results: A total of 296 moderate and 320 severe pts were included in this analysis. Baseline pt characteristics were similar between groups, but with slightly higher prior immunomodulator use in severe vs moderate pts (Table). OZA was more effective than PBO in achieving all efficacy endpoints at W10; treatment differences (OZA [C1] vs PBO) were greater in moderate vs severe pts for all endpoints (Figure 1A). More OZA/OZA vs OZA/PBO pts achieved clinical and mucosal efficacy at W52; treatment differences (OZA/OZA vs OZA/PBO) were slightly greater in moderate vs severe pts for all endpoints except endoscopic improvement (Figure 1B). Eighty-two W52 OZA/OZA responders entered the OLE (moderate, n=45; severe, n=37); efficacy rates at OLE W46 were similar in moderate and severe pts and were maintained through OLE W94 in the observed case analysis (Figure 1C). Overall, the data followed similar patterns in the nonresponder imputation analyses across endpoints.

Discussion: OZA was efficacious and durable in AT-naive UC pts whose disease was inadequately controlled on CTs. Pts with moderate disease benefitted more from OZA during the first year of therapy, especially during induction, but long-term durability of OZA for up to 3 years was similar in moderate and severe OZA clinical responders. OZA may be an appropriate oral AT option for achieving and sustaining long-term benefit in AT-naive UC pts.

Figure: Figure 1. Efficacy during TN IP, TN MP, and TN OLE in AT-naive pts by baseline endoscopic disease activity.

	AT-naive moderate^a			AT-naive severe^b
	PBO (C1) n=64	OZA (C1) n=138	OZA (C2) n=94	PBO (C1) n=73	OZA (C1) n=149	OZA (C2) n=98
Age, y, mean (SD)	42.6 (13.6)	41.9 (13.2)	42.9 (14.9)	42.7 (14.1)	41.8 (13.4)	45.1 (12.8)
Males, n (%)	38 (59.4)	78 (56.5)	54 (57.4)	52 (71.2)	86 (57.7)	64 (65.3)
Years since UC diagnosis, mean (SD)	6.3 (7.0)	5.5 (5.9)	6.0 (7.4)	5.9 (7.4)	5.9 (6.0)	8.0 (8.5)
Extensive disease, n (%)	16 (25.0)	41 (29.7)	21 (22.3)	31 (42.5)	52 (34.9)	32 (32.7)
CS use at screening, n (%)	18 (28.1)	23 (16.7)	20 (21.3)	21 (28.8)	40 (26.8)	24 (24.5)
Prior 5-ASA use, n (%)	62 (96.9)	135 (97.8)	94 (100.0)	72 (98.6)	146 (98.0)	98 (100.0)
Prior CS use, n (%)	42 (65.6)	92 (66.7)	57 (60.6)	47 (64.4)	96 (64.4)	66 (67.3)
Prior IMM use, n (%)	15 (23.4)	27 (19.6)	12 (12.8)	18 (24.7)	50 (33.6)	22 (22.4)

Table. Demographic and clinical characteristics at baseline in the IP of AT-naive pts by baseline endoscopic disease activity.
^aModerate pts had MES=2 at baseline. ^bSevere pts had MES=3 at baseline. 5-ASA, 5-aminosalicylate; CS, corticosteroid; IMM, immunomodulator.

Disclosures:

David T. Rubin: AbbVie – Consultant. Alike Health – Stock Options. AltruBio – Consultant, Stock Options. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Chronicles – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Cornerstones Health, Inc – Advisory Committee/Board Member. Crohn's & Colitis Foundation – Advisory Committee/Board Member. Datos Health – Stock Options. EcoR1 – Consultant. Eli Lilly – Consultant. GastroIntestinal Research Foundation – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant. Helmsley Charitable Trust – Grant/Research Support. Iterative Health – Consultant. Iterative Health – Stock Options. Janssen – Consultant. Kaleido Biosciences – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Reistone – Consultant. Seres Therapeutics – Consultant. Syneos – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Trellus Health – Consultant.

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.

Geert D’Haens: AbbVie – Advisor or Review Panel Member, Speakers Bureau. Agomab Therapeutics – Advisor or Review Panel Member. Alimentiv – Advisor or Review Panel Member. Applied Molecular Therapeutics – Advisor or Review Panel Member. AstraZeneca – Advisor or Review Panel Member. Boehringer Ingelheim – Advisor or Review Panel Member. Bristol Myers Squibb – Advisor or Review Panel Member, Speakers Bureau. Celltrion – Advisor or Review Panel Member. Cytoki – Advisor or Review Panel Member. Eli Lilly – Advisor or Review Panel Member, Speakers Bureau. Exeliom – Advisor or Review Panel Member. Ferring – Advisor or Review Panel Member. Galapagos – Advisor or Review Panel Member, Speakers Bureau. GlaxoSmithKline – Advisor or Review Panel Member. Gossamer Bio – Advisor or Review Panel Member. Immunic – Advisor or Review Panel Member. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. Pfizer – Advisor or Review Panel Member, Speakers Bureau. Polpharma – Advisor or Review Panel Member. ProciseDx – Advisor or Review Panel Member. Progenity – Advisor or Review Panel Member. Prometheus Biosciences – Advisor or Review Panel Member. Prometheus Laboratories – Advisor or Review Panel Member. Protagonist Therapeutics – Advisor or Review Panel Member. Seres – Advisor or Review Panel Member. Takeda – Advisor or Review Panel Member, Speakers Bureau. Tillotts – Advisor or Review Panel Member, Speakers Bureau. Versant – Advisor or Review Panel Member.

Peter Irving: AbbVie – Advisory Committee/Board Member, lecture fees. Arena – Advisory Committee/Board Member. Boehringer-Ingelheim – Advisory Committee/Board Member. Bristol Myers Squibb – Advisory Committee/Board Member, lecture fees. Celgene – Advisory Committee/Board Member, lecture fees. Celltrion – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Eli Lilly – Advisory Committee/Board Member, lecture fees. Falk Pharma – lecture fees. Ferring – lecture fees. Galapagos – Grant/Research Support, lecture fees. Genetech – Advisory Committee/Board Member. Gilead – Advisory Committee/Board Member, lecture fees. Hospira – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member, lecture fees. MSD – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Pfizer – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Pharmacosmos – Advisory Committee/Board Member. Prometheus – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Samsung Bioepis – Advisory Committee/Board Member. Sandoz – Advisory Committee/Board Member, lecture fees. Sapphire Medical – lecture fees. Shire – lecture fees. Takeda – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Tillots – lecture fees. Topivert – Advisory Committee/Board Member. VH2 – Advisory Committee/Board Member. Vifor Pharma – Advisory Committee/Board Member. Warner Chilcott – Advisory Committee/Board Member, lecture fees.

Irina Blumenstein: AbbVie – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. Arena – Consultant, Speakers Bureau. Biogen – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Celgene – Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Mylan – Speakers Bureau. Pfizer – Consultant. Shire – Consultant. Takeda – Consultant, Speakers Bureau.

Corey Siegel: Abbvie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. BMS – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Fresnius – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Consultant/advisory board, speaker for CME activities. Napo Pharmaceuticals – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, speaker for CME activities. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau.

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.

Douglas C. Wolf: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. AstraZeneca – Grant/Research Support. Bristol Myers Squibb – Consultant, Grant/Research Support, Speakers Bureau. Eli Lilly – Consultant. Genentech – Grant/Research Support. Janssen – Consultant, Grant/Research Support, Speakers Bureau. Pfizer – Consultant. Pfizer/Arena – Grant/Research Support. Takeda – Consultant, Grant/Research Support, Speakers Bureau.

Bincy Abraham: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Celltrion – Consultant. Eli Lilly – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Medtronics – Consultant. Pfizer – Consultant, Speakers Bureau. Samsung Bioepis – Consultant. Takeda – Consultant, Grant/Research Support, Speakers Bureau.

Freddy Caldera: Arena – Consultant. Celgene – Consultant. GlaxoSmithKline – Consultant. Janssen – Grant/Research Support. Novavax – Grant/Research Support. Takeda – Consultant, Grant/Research Support.

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.

Anjali Jain: Bristol Myers Squibb – employee and/or shareholder.

Hsiuanlin Wu: Bristol Myers Squibb – employee and/or shareholder.

Mark T. Osterman: Bristol Myers Squibb – employee and/or shareholder.

Millie D. Long: AbbVie – Consultant. Bristol Myers Squibb – Consultant. Eli Lilly – Consultant, Grant/Research Support. Genentech – Consultant. Intercept – Consultant. Janssen – Consultant. Pfizer – Consultant, Grant/Research Support. Prometheus – Consultant. Roche – Consultant. Salix – Consultant. Takeda – Consultant, Grant/Research Support. Target PharmaSolutions – Consultant. UCB – Consultant. Valeant – Consultant.

David T. Rubin, MD, FACG¹, Britta Siegmund, MD, PhD², Geert R. D’Haens, PhD³, Peter M.. Irving, MD⁴, Irina Blumenstein, MD, PhD⁵, Corey A. Siegel, MD, MS⁶, Edward V.. Loftus, MD⁷, Douglas C. Wolf, MD, FACG⁸, Bincy Abraham, MD, MS, FACG⁹, Freddy Caldera, DO, MS¹⁰, Laurent Peyrin-Biroulet, MD, PhD¹¹, Anjali Jain, PhD¹², Hsiuanlin Wu, MS¹², Mark T. Osterman, MD, PhD¹², Millie D. Long, MD, MPH¹³. P0729 - Efficacy and Durability of Ozanimod by Baseline Endoscopic Disease Activity in Advanced Therapy–Naive Ulcerative Colitis Patients Suboptimally Controlled on Conventional Therapies, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.