Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II

• Published in: Journal of Crohn's and colitis Vol. 15; no. 6; pp. 938 - 949
• Main Authors: Reinisch, Walter, Sandborn, William J, Danese, Silvio, Hébuterne, Xavier, Kłopocka, Maria, Tarabar, Dino, Vaňásek, Tomáš, Greguš, Miloš, Hellstern, Paul A, Kim, Joo Sung, Sparrow, Miles P, Gorelick, Kenneth J, Hoy, Michael, Goetsch, Martina, Bliss, Caleb, Gupta, Charu, Cataldi, Fabio, Vermeire, Séverine
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 18.02.2021
• Subjects: Original; MAdCAM-1; phase 2; Ulcerative colitis
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjab023

Abstract Background and Aims Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. Methods TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator’s discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. Results Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. Conclusions Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.