IBD

11 - A Randomized, Double-Blind, Placebo-Controlled Trial of a Selective, Oral Sphingosine 1-Phosphate (S1P) Receptor Modulator, Etrasimod (APD334), in Moderate to Severe Ulcerative Colitis (UC): Results From the OASIS Study

Monday, October 8
2:15 PM - 2:25 PM
Location: Terrace Ballroom 4 (level 400)

Category: IBD
William J. Sandborn, MD, FACG1, Laurent Peyrin-Biroulet, MD, PhD2, Luba Trokan3, Jinkun Zhang3, Tanja Kühbacher, MD, PhD4, Michael Chiorean, MD5, Scott D. Lee, MD6, Severine Vermeire, MD, PhD7, Bruce Yacyshyn, MD, FACG8, Snehal Naik3, Preston Klassen3, Julian Panes, PhD9
1University of California San Diego, La Jolla, CA; 2University Hospital of Nancy, University of Lorraine, Nancy, Lorraine, France; 3Arena Pharmaceuticals, San Diego, CA; 4Asklepio Westklinikum, Hamburg, Germany; 5Virginia Mason Medical Center, Seattle, WA; 6University of Washington, Seattle, WA; 7University Hospitals Leuven, Leuven, Brussels Hoofdstedelijk Gewest, Belgium; 8University of Cincinnati, Cincinnati, OH; 9Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain

Award: ACG Auxiliary Award (Member)

Introduction: The efficacy and safety of etrasimod, a selective, oral S1P receptor 1, 4, and 5 modulator, was evaluated in patients (pts) with moderate-severe UC.

Methods: This randomized, double-blind, parallel-group, 12-week (wk) phase 2 induction study evaluated etrasimod in pts with moderate-severe UC, defined as 3-component Mayo Clinic Score (MCS) of 4–9 with endoscopic subscore ≥2 and rectal bleeding (RB) subscore ≥1. The 3-component MCS (range 0–9) includes RB, stool frequency, and endoscopy. Pts received once-daily etrasimod 1 mg (n=52) or 2 mg (n=50), with no dose titration, or placebo (PBO; n=54). The primary endpoint (EP) was change from baseline (BL) in 3‑component MCS at wk 12. Secondary EPs included the proportion of pts with endoscopic remission (≤1 point). Exploratory EPs included the proportion of pts achieving clinical remission and clinical response at wk 12 and change in lymphocyte count (LC). Changes in MCS were assessed by analysis of covariance with treatment as a factor and current oral corticosteroid (CS)use, prior anti-tumor necrosis factor (TNF)α use, and BL measures as covariates; LC was assessed by mixed-effects model and parameters with proportions of pts by the Mantel-Haenszel method with adjustment for current oral CS and prior anti-TNFα use.

Results: Of 156 pts randomized, 90% completed the study. BL characteristics, including age, sex, disease duration, current CS use, prior biologic use, were balanced among groups. At wk 12, dose-dependent improvement occurred with etrasimod in all efficacy measures vs PBO (Table). Etrasimod 2 mg improved change from BL in 3-component MCS vs PBO (difference, 0.99 points; 90% CI, 0.30–1.68; P=0.009) (Figure). More pts receiving etrasimod 2 mg achieved endoscopic improvement (41.8% vs 17.8% for PBO; P=0.003). At wk 12, there was a significant decrease in circulating LCs from BL with etrasimod 1 and 2 mg relative to PBO (37.2% and 57.3%, respectively; P < 0.001 for both). Adverse events (AEs) were mostly mild to moderate and similar among groups. More PBO-treated pts (11.1%) had a serious AE (SAE) vs etrasimod-treated pts (2 mg, 0%; 1 mg, 5.8%), reflecting disease worsening. No SAEs related to bradycardia or atrioventricular block were noted.

Discussion: In pts with moderate-severe UC, etrasimod was more effective than PBO in achieving dose-dependent improvements in clinical response, clinical remission, and endoscopic appearance. Etrasimod was safe and well tolerated in this short-term study.


Disclosures:
William Sandborn: Abbvie – Consultant, Grant/Research Support, Speaker's Bureau. Akros Pharma – Consultant. Allergan – Consultant. Ambrx Inc. – Consultant. Amgen – Consultant, Grant/Research Support. Ardelyx – Consultant. Arena Pharmaceuticals – Consultant. Atlantic Healthcare Limited – Grant/Research Support. Atlantic Pharmaceuticals – Consultant. Avaxia – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Meyers Squibb – Consultant. Celgene – Consultant. Celgene/Receptos – Grant/Research Support. Conatus – Consultant. Cosmo Technologies – Consultant. Escalier Biosciences – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Ferring – Consultant. Ferring Research Institute – Consultant. Forward Pharma – Consultant. Galapagos – Consultant. Genentech – Consultant, Grant/Research Support. Gilead Sciences – Consultant, Grant/Research Support. Immune Pharmaceuticals – Consultant. Index Pharmaceuticals – Consultant. Janssen – Consultant, Grant/Research Support, Speaker's Bureau. Kyowa Hakko Kirin Pharma – Consultant. Lilly – Consultant, Grant/Research Support. MedImmune – Consultant. Mesoblast – Consultant. Miraca Life Sciences – Consultant. Nivalis Therapeutics – Consultant. Novartis – Consultant. Nutrition Science Partners – Consultant. Oppilan Pharma – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Otsuka – Consultant. Palatin – Consultant. Paul Hastings – Consultant. Pfizer – Consultant. Precision IBD – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Progenity – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Prometheus Laboratories – Consultant. Qu Biologics – Consultant. Regeneron – Consultant. Ritter Pharmaceuticals – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Robarts Clinical Trials (owned by the University of Western Ontario) – Consultant. Salix – Consultant. Seattle Genetics – Consultant. Seres Therapeutics – Consultant. Shire – Consultant. Sigmoid Biotechnologies – Consultant. Takeda – Consultant, Grant/Research Support, Speaker's Bureau. Theradiag – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant. UCB Pharma – Consultant. Vascular Biogenics – Consultant. Vivelix – Consultant.
Laurent Peyrin-Biroulet: AbbVie – Consultant, Grant/Research Support, Lecture Fees . Biogen – Lecture Fees. Boehringer Ingelheim – Consultant. Celgene – Consultant. Genentech – Consultant. GlaxoSmithKline – Consultant. Janssen – Consultant, Lecture Fees. Merck Sharp & Dohme – Consultant, Grant/Research Support, Lecture Fees . Oppilan – Consultant. Pfizer – Consultant, Lecture Fees. Roche – Consultant. Shire – Consultant, Lecture Fees. Takeda – Consultant, Grant/Research Support, Lecture Fees. Theravance – Consultant. TiGenix – Consultant.
Luba Trokan: Arena – Employee.
Jinkun Zhang: Arena – Employee.
Tanja Kühbacher indicated no relevant financial relationships.
Michael Chiorean: AbbVie – Speaker's Bureau. Arena – Advisory Committee/Board Member. Janssen – Speaker's Bureau. Medtronic – Speaker's Bureau. Pfizer – Advisory Committee/Board Member, Consultant. Salix – Consultant. Takeda – Grant/Research Support, Speaker's Bureau.
Scott Lee: AbbVie Pharmaceuticals – Grant/Research Support. Arena Pharmaceuticals – Grant/Research Support. Atlantic Pharmaceuticals, Ltd. – Grant/Research Support. Celgene Pharmaceuticals, Inc. – Grant/Research Support. Cornerstones Health – Advisory Committee/Board Member, Consultant. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. Janssen Pharmaceuticals, Inc. – Advisory Committee/Board Member, Consultant, Grant/Research Support. Pfizer Pharmaceuticals – Advisory Committee/Board Member, Consultant. Salix Pharmaceuticals – Grant/Research Support. Shield Therapeutics PLC – Grant/Research Support. Takeda Pharmaceuticals, Inc. – Grant/Research Support. Tetherex Pharmaceuticals – Grant/Research Support. UCB Pharma – Advisory Committee/Board Member, Consultant, Grant/Research Support.
Severine Vermeire: Abbvie – Consultant, Grant/Research Support. Biogen – Consultant. Celgene – Consultant. Ferring Pharmaceuticals – Consultant. Galagapos – Consultant. Gilead – Consultant. Hospira – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Second Genome – Consultant. Takeda – Consultant, Grant/Research Support.
Bruce Yacyshyn: Merck – Grant/Research Support.
Snehal Naik: Arena – Employee.
Preston Klassen: Arena – Employee.
Julian Panes: AbbVie – Consultant, Grant/Research Support, Lecture Fees. Biogen – Lecture Fees. Boehringer Ingelheim – Consultant. Celgene – Consultant. Genentech – Consultant. Janssen – Consultant, Lecture Fees. Merck Sharp & Dohme – Consultant, Grant/Research Support, Lecture Fees. Oppilan – Consultant. Pfizer – Consultant, Lecture Fees. Roche – Consultant. Shire – Consultant, Lecture Fees. Takeda – Consultant, Lecture Fees. Theravance – Consultant. TiGenix – Consultant.

William J. Sandborn

Professor of Clinical Medicine
University of California - San Diego, San Diego, CA, United States
La Jolla, CA, US

Dr. William Sandborn completed medical school and an internal medicine residency at Loma Linda University in Loma Linda California. He completed a gastroenterology fellowship at the Mayo Clinic in Rochester Minnesota in 1993. From 1993-2010, he was on the faculty of the Mayo Clinic, rising to Professor of Medicine, Vice Chairman of the Division of Gastroenterology and Hepatology, and Associate Dean of Research for Intellectual Property and Industry Relations. In 2011 he became Professor of Clinical Medicine at the University of California San Diego and Director of the IBD Center and Chief of the Division of Gastroenterology for the UC San Diego Health System. Dr. Sandborn has published over 405 peer reviewed articles including articles in the New England Journal of Medicine, the Lancet, JAMA, the Annals of Internal Medicine, and Gastroenterology. His research interests are clinical trials and clinical pharmacology related to inflammatory bowel disease.

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11 - A Randomized, Double-Blind, Placebo-Controlled Trial of a Selective, Oral Sphingosine 1-Phosphate (S1P) Receptor Modulator, Etrasimod (APD334), in Moderate to Severe Ulcerative Colitis (UC): Results From the OASIS Study



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Send Email for A Randomized, Double-Blind, Placebo-Controlled Trial of a Selective, Oral Sphingosine 1-Phosphate (S1P) Receptor Modulator, Etrasimod (APD334), in Moderate to Severe Ulcerative Colitis (UC): Results From the OASIS Study