Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn's Disease: The OPERA II Study

Inflamm Bowel Dis. 2022 Jul 1;28(7):1034-1044. doi: 10.1093/ibd/izab215.


Geert R D'Haens 1Walter Reinisch 2Scott D Lee 3Dino Tarabar 4Edouard Louis 5Maria Klopocka 6Jochen Klaus 7Stefan Schreiber 8Dong Il Park 9Xavier Hébuterne 10Peter Nagy 11Fabio Cataldi 12Steven W Martin 13Satyaprakash Nayak 13Anindita Banerjee 13Kenneth J Gorelick 14William J Sandborn 15


Author information

1Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.

2Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

3Division of Gastroenterology, University of Washington, Seattle, WA, USA.

4Clinic of Gastroenterology and Hepatology, Military Medical Academy, Belgrade, Serbia.

5Department of Clinical Sciences, University Hospital Centre Hospitalier Universitaire of Liège, Liège, Belgium.

6Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.

7Clinic for Internal Medicine, University Hospital Ulm, Ulm, Germany.

8Clinic for Internal Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University of Kiel, Kiel, Germany.

9Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.

10University Côte d'Azur, Centre Hospitalier Universitaire of Nice, Nice, France.

11Shire, a Takeda company, Zug, Switzerland.

12Shire, a Takeda company, Lexington, MA, USA.

13Pfizer, Cambridge, MA, USA.

14Zymo Consulting Group, Newtown Square, PA, USA.

15Medicine, University of California San Diego, La Jolla, CA, USA.


Background: Patients with Crohn's disease (CD) experience intestinal inflammation. Ontamalimab (SHP647), a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, is a potential novel CD treatment. OPERA II, a multicenter, open-label, phase 2 extension study, assessed the long-term safety and efficacy of ontamalimab in patients with moderate-to-severe CD.

Methods: Patients had completed 12 weeks of blinded treatment (placebo or ontamalimab at 22.5, 75, or 225 mg subcutaneously) in OPERA (NCT01276509) or had a clinical response to ontamalimab 225 mg in TOSCA (NCT01387594). Participants received ontamalimab at 75 mg every 4 weeks (weeks 0-72), then were followed up every 4 weeks for 24 weeks. One-time dose reduction to 22.5 mg or escalation to 225 mg was permitted at the investigator's discretion. The primary end points were safety and tolerability outcomes. Secondary end points included changes in serum drug and biomarker concentrations. Efficacy end points were exploratory, and used non-responder imputation methods.

Results: Overall, 149/268 patients completed the study. The most common adverse event leading to study discontinuation was CD flare (19.8%). Two patients died; neither death was considered to be drug related. No dose reductions occurred; 157 patients had their dose escalated. Inflammatory biomarker concentrations decreased. Serum ontamalimab levels were consistent with known pharmacokinetics. Remission rates (Harvey-Bradshaw Index [HBI] ≤ 5; baseline, 48.1%; week 72, 37.3%) and response rates (baseline [decrease in Crohn's Disease Activity Index ≥ 70 points], 63.1%; week 72 [decrease in HBI ≥ 3], 42.5%) decreased gradually.

Conclusions: Ontamalimab was well tolerated; treatment responses appeared to be sustained over 72 weeks.ClinicalTrials.gov ID: NCT01298492.


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