Back

P1417 - Long-Term Mucosal Healing, Clinical Response and Clinical Remission in Patients With Ulcerative Colitis Treated With the Anti-MAdCAM-1 Antibody Ontamalimab: Results From the Open-Label Extension Study TURANDOT II

Monday, October 28

10:30 AM - 4:15 PM

Location: Exhibit Halls 3 and 4 (Street Level)

Presenting Author(s)

William Sandborn, MD

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

Silvio Danese, MD, PhD¹, William J. Sandborn, MD, FACG², Walter Reinisch, MD³, Xavier Hébuterne, MD⁴, Maria Kłopocka, MD, PhD⁵, Dino Tarabar, MD, PhD⁶, Tomáš Vaňásek, MD, PhD⁷, Miloš Greguš, MD⁸, Paul A. Hellstern, MD⁹, Joo Sung Kim, PhD, MD, MS¹⁰, Miles Sparrow, MD, PhD, MBBS¹¹, Kenneth J. Gorelick, MD¹², Martina Goetsch, MD¹³, Caleb Bliss, PhD¹⁴, Charu Gupta, MS¹⁵, Fabio Cataldi, MD¹⁴, Séverine Vermeire, MD, PhD¹⁶

¹Humanitas University, Milan, Lombardia, Italy; ²University of California San Diego, La Jolla, CA; ³Medical University of Vienna, Vienna, Wien, Austria; ⁴Université de Nice-Sophia-Antipolis, Nice, Provence-Alpes-Cote d'Azur, France; ⁵Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Kujawsko-Pomorskie, Poland; ⁶Military Medical Academy, Belgrade, Vojvodina, Serbia; ⁷Charles University Hospital, Hradec Králové, Kralovehradecky kraj, Czech Republic; ⁸Gastroenterology Center, Nitra, Nitra, Slovakia; ⁹Nature Coast Clinical Research, Inverness, FL; ¹⁰Seoul National University College of Medicine, Seoul, Seoul-t'ukpyolsi, Republic of Korea; ¹¹Alfred Hospital, Melbourne, Victoria, Australia; ¹²Zymo Consulting Group, Newtown Square, PA; ¹³Shire, a Takeda company, Zug, Zug, Switzerland; ¹⁴Shire, a Takeda company, Lexington, MA; ¹⁵Cytel Inc., Cambridge, MA; ¹⁶University Hospitals, Leuven, Vlaams-Brabant, Belgium

Introduction: Ontamalimab (SHP647), a human monoclonal IgG₂ antibody, targets mucosal addressin cell adhesion molecule-1 (MAdCAM-1), to reduce lymphocyte homing to the gastrointestinal (GI) tract. In the TURANDOT II trial, ontamalimab was well-tolerated and clinical benefit was seen up to 144 wks in patients with ulcerative colitis (UC). Here we report long-term mucosal healing, response and remission in a subset of patients in TURANDOT II.

Methods: TURANDOT II (NCT01771809) is a phase 2, 2-part open-label (OL) extension study of ontamalimab in patients with UC who received placebo or ontamalimab 7.5, 22.5, 75 or 225mg in the feeder study (TURANDOT). At TURANDOT II baseline (TURANDOT wk 12), patients were randomized to ontamalimab 75 or 225mg every 4 wks for 72 wks (OL1). In cases of clinical exacerbation or no response, escalation from 75 to 225mg was permitted from wk 8. In OL2, patients received 75mg every 4 wks for 72 wks. Endoscopies were carried out at wk 16, and a subset of patients undergoing routine cancer surveillance had at least one follow-up endoscopy between wks 40 and 72 of OL1: all endoscopies were centrally-read. Mucosal healing (Mayo endoscopy subscore ≤1), clinical remission (total Mayo score ≤2, no subscore >1) and clinical response (≥3-point decrease in total Mayo score from TURANDOT baseline, ≥30% change; ≥1-point decrease in or ≤1 rectal bleed absolute score) were measured.

Results: Of 330 patients in TURANDOT II, 101 had follow-up endoscopies (Table 1), 25.7% (n=26) of whom had mucosal healing at TURANDOT II baseline. At wk 16, 43.6% (n=44) had mucosal healing, and 33 of these patients (75%) maintained mucosal healing up to wk 40–72. Of 65 responders in TURANDOT, 37 (56.9%) had mucosal healing at both wk 16 and wk 40–72. Of 36 non-responders, 7 (19.4%) and 9 (25%) achieved mucosal healing at wk 16 and wk 40–72, respectively (Figure 1). Of the responders, 58 (89.2%) maintained response and 27 (41.5%) were in remission at wk 16; at wk 40–72, 53 (81.5%) maintained response and 33 (50.8%) were in remission. Of non-responders, 22 (61.1%) achieved response and 5 (13.9%) achieved remission by wk 16; by wk 40–72, 17 (47.2%) had responded and 8 (22.2%) were in remission. Overall, the mean Mayo endoscopic subscore of 2 (SD, 0.1) was maintained to wk 40–72.

Discussion: Mucosal healing, response and remission persisted in a subset of patients who continued ontamalimab treatment up to 72 wks and underwent surveillance endoscopies between wks 40 and 72.

Table 1. Patient demographics and characteristics at TURANDOT II baseline. SD, standard deviation; TNF, tumour necrosis factor; UC, ulcerative colitis; FC, fecal calprotectin a) Time since UC diagnosis was derived as: ([Date of Visit 1 in TURANDOT II – date of diagnosis from TURANDOT] + 1) / 365.25. b) Calculated for patients included in the pharmacodynamic analyses only (n=98).

Figure 1. Proportion of patients (%) demonstrating mucosal healing at baseline, week 12 and week 40–72.

Disclosures:

Silvio Danese: Abbott Laboratories – Consultant. AbbVie – Consultant. AstraZeneca – Consultant. Ferring – Lecturer. Millennium – Consultant. MSD – Advisory Committee/Board Member, Lecturer. Schering Plough – Consultant. Takeda – Consultant. UCB Pharma – Lecturer.

William Sandborn: AbbVie – Grant/Research Support, Personal fees. Actavis – Personal fees. Actogenix NV – Personal fees. Adheron Therapeutics – Personal fees. Akros Pharma – Personal fees. Ambrx Inc. – Personal fees. Amgen – Personal fees. AM-Pharma BV – Personal fees. Ardelyx Inc. – Personal fees. Arena Pharmaceuticals – Personal fees. Atlantic Pharmaceuticals – Grant/Research Support, Personal fees. Avaxia Biologics – Personal fees. Baxter Healthcare – Personal fees. Biogen – Personal fees. Boehringer Ingelheim – Grant/Research Support, Personal fees. Bristol-Myers Squibb – Grant/Research Support, Personal fees. Catabasis Pharmaceuticals – Personal fees. Celgene – Personal fees. Celgene Cellular Therapeutics – Personal fees. Chiasma – Personal fees. Cosmo Pharmaceuticals – Personal fees. Dr August Wolff – Personal fees. Eisai – Personal fees. Eli Lilly – Personal fees. Ferring – Personal fees. Ferring Research Institute – Personal fees. Forward Pharma – Personal fees. Galagapos NV – Personal fees. Genentech – Grant/Research Support, Personal fees. Gilead Sciences – Personal fees. Immune Pharmaceuticals – Personal fees. InDex Pharmaceuticals – Personal fees. Ironwood Pharmaceuticals – Personal fees. Janssen – Grant/Research Support, Personal fees. Kyowa Hakko Kirin – Personal fees. Lexicon Pharmaceuticals – Personal fees. Lipid Therapeutics GmbH – Personal fees. Luitpoild, MedImmune (AstraZeneca) – Personal fees. Mesoblast Inc – Personal fees. Millennium Pharmaceuticals – Personal fees. Nestlé – Personal fees. Novo Nordisk – Personal fees. Nutrition Science Partners – Grant/Research Support, Personal fees. Orexigen – Personal fees. Palatin – Personal fees. Pfizer – Consultant. Prometheus Laboratories – Grant/Research Support, Personal fees. Qu Biologics – Personal fees. Regeneron – Personal fees. Ritter Pharmaceuticals – Personal fees. Salix Pharmaceuticals – Personal fees. Santarus – Personal fees. Seattle Genetics – Personal fees. Seres Health – Personal fees. Shire – Consultant, Grant/Research Support, Personal fees. Sigmoid Biotechnologies – Personal fees. Takeda – Grant/Research Support, Personal fees. Teva Pharmaceuticals – Personal fees. Theradiag – Personal fees. Theravance – Personal fees. TiGenix – Personal fees. Tillotts Pharma – Personal fees. Toray Industries Inc. – Personal fees. UCB Pharma – Personal fees. Vascular Biogenics – Personal fees. Vertex Pharmaceuticals – Personal fees. Warner Chilcott – Personal fees. Western University (owner of Robarts Clinical Trials) – Personal fees. Zyngenia – Personal fees.

Walter Reinisch: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker. Amgen – Advisory Committee/Board Member, Consultant. Astellas – Advisory Committee/Board Member, Consultant, Speaker. Avaxia – Consultant. BioClinica – Consultant. Biogen Idec – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Bristol-Myers Squibb – Advisory Committee/Board Member. Celgene – Advisory Committee/Board Member, Consultant. Cellerix – Advisory Committee/Board Member. Celltrion – Advisory Committee/Board Member, Consultant, Speaker. Covance – Consultant. Dohme – Advisory Committee/Board Member, Consultant, Speaker. Dr. Falk Pharma GmbH – Consultant. Ferring – Consultant, Speaker. Galapagos NV – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead Sciences – Consultant. ICON – Consultant. InDex Pharmaceuticals – Consultant. Inova – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speaker. Johnson – Advisory Committee/Board Member, Consultant. Lipid Therapeutics – Consultant. LivaNova – Consultant. Mallinckrodt – Consultant. MedImmune – Consultant. Merck Sharp – Advisory Committee/Board Member, Consultant, Speaker. Millennium – Consultant. Mitsubishi Tanabe Pharma Corporation – Advisory Committee/Board Member, Consultant, Speaker. MSD – Grant/Research Support. Novartis – Consultant. Parexel – Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Speaker. Pharmacosmos – Advisory Committee/Board Member, Consultant, Speaker. Philip Morris Institute – Consultant. Provention Bio – Consultant. Robarts Clinical Trials – Consultant. Roland Berger GmBH – Consultant. Sandoz – Advisory Committee/Board Member, Consultant. Schering-Plough – Advisory Committee/Board Member, Consultant, Speaker. Second Genome – Consultant. Seres Therapeutics – Consultant. Shire – Speaker. Sigmoid – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speaker. Therakos – Consultant, Speaker. TiGenix – Consultant. Zealand – Advisory Committee/Board Member, Consultant.

Xavier Hébuterne: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Lecturer. Abivax – Advisory Committee/Board Member, Grant/Research Support. Alphasigma – Grant/Research Support. ARARD – Lecturer. Arkopharma – Advisory Committee/Board Member, Lecturer. Astellas – Advisory Committee/Board Member. Baxter – Lecturer. Bristol Myers Squibb – Lecturer. Cellgène – Grant/Research Support. Eli Lilly – Grant/Research Support. Enterome – Grant/Research Support. Ferring – Lecturer. Gilead – Grant/Research Support. InDex Pharmaceuticals – Grant/Research Support. Janssen – Advisory Committee/Board Member, Grant/Research Support, Lecturer. MSD – Lecturer. Nutricia – Advisory Committee/Board Member, Lecturer. Pfizer – Advisory Committee/Board Member, Grant/Research Support, Lecturer. Roche – Advisory Committee/Board Member, Grant/Research Support. Salix – Grant/Research Support. Sanofi-Advantis – Lecturer. Takeda – Advisory Committee/Board Member, Grant/Research Support, Lecturer. Theravance – Grant/Research Support. Tillots – Lecturer.

Maria Kłopocka: AbbVie – Speaker, congress support. Egis – Grant/Research Support, Speaker, congress support. Ferring – Speaker, congress support. Sanofi – Speaker. Takeda – Speaker.

Dino Tarabar: AbbVie – Lecturer. Amicus – Grant/Research Support. Dohme – Lecturer. Ferring – Lecturer. Merck Sharp – Lecturer. Pfizer – Consultant, Lecturer. Roche – Grant/Research Support, Lecturer. Sandoz – Lecturer. Takeda – Lecturer.

Tomáš Vaňásek: Hospira – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member.

Miloš Greguš: AbbVie – Consultant, Speaker. Alfa Wasserman – Consultant, Speaker. Alfa Wasserman – Development of educational materials. Egis – Development of educational materials. Ferring – Consultant, Speaker. Hospira – Consultant, Speaker, Development of educational materials. Janssen – Consultant, Speaker. MSD – Consultant, Speaker, Development of educational materials. Pfizer – Consultant, Speaker. Takeda – Consultant, Speaker, Development of educational materials. Vifor – Development of educational materials.

Paul Hellstern: Nature Coast Clinical Research – Employee.

Joo Sung Kim indicated no relevant financial relationships.

Miles Sparrow: AbbVie – Advisory Committee/Board Member, Speaker. Celgene – Advisory Committee/Board Member. Ferring – Advisory Committee/Board Member, Grant/Research Support. Janssen – Advisory Committee/Board Member, Speaker. MSD – Advisory Committee/Board Member. Orphan – Grant/Research Support. Pfizer – Advisory Committee/Board Member, Speaker. Shire – Speaker. Takeda – Advisory Committee/Board Member, Speaker.

Kenneth Gorelick: Pfizer – Consultant. Shire – Consultant.

Martina Goetsch: Shire – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Caleb Bliss: Cytel Inc. – Employee. Shire – Consultant.

Charu Gupta: Cytel Inc – Employee.

Fabio Cataldi: Pfizer – Previous employee. Shire – Stockholder/Ownership Interest (excluding diversified mutual funds), Previous employee.

Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. Biogen – Consultant. Celgene – Consultant. Ferring – Consultant. Galagapos NV – Consultant. Gilead Sciences – Consultant. Hospira – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Second Genome – Consultant. Shire – Consultant. Takeda – Consultant, Grant/Research Support.

Citation: Silvio Danese, MD, PhD; William J. Sandborn, MD, FACG; Walter Reinisch, MD; Xavier Hébuterne, MD; Maria Kłopocka, MD, PhD; Dino Tarabar, MD, PhD; Tomáš Vaňásek, MD, PhD; Miloš Greguš, MD; Paul A. Hellstern, MD; Joo Sung Kim, PhD, MD, MS; Miles Sparrow, MD, PhD, MBBS; Kenneth J. Gorelick, MD; Martina Goetsch, MD; Caleb Bliss, PhD; Charu Gupta, MS; Fabio Cataldi, MD; Séverine Vermeire, MD, PhD. P1417 - LONG-TERM MUCOSAL HEALING, CLINICAL RESPONSE AND CLINICAL REMISSION IN PATIENTS WITH ULCERATIVE COLITIS TREATED WITH THE ANTI-MADCAM-1 ANTIBODY ONTAMALIMAB: RESULTS FROM THE OPEN-LABEL EXTENSION STUDY TURANDOT II. Program No. P1417. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.