Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: The OPERA study

Masayuki Saruta, Dong Il Park, Young Ho Kim, Suk Kyun Yang, Byung Ik Jang, Jae Hee Cheon, Jong Pil Im, Takanori Kanai, Tatsuro Katsuno, Yoh Ishiguro, Makoto Nagaoka, Naoki Isogawa, Yinhua Li, Anindita Banerjee, Alaa Ahmad, Mina Hassan-Zahraee, Robert Clare, Kenneth J. Gorelick, Fabio Cataldi, Mamoru WatanabeToshifumi Hibi

Research output: Contribution to journalArticle

Abstract

Background/Aims: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD). Methods: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein >3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn's Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. Results: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. Conclusions: In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results.

Original languageEnglish
Pages (from-to)45-55
Number of pages11
JournalIntestinal Research
Volume18
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

Keywords

  • Crohn disease
  • Japanese
  • Korean
  • MAdCAM
  • PF-00547659

ASJC Scopus subject areas

  • Gastroenterology

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    Saruta, M., Park, D. I., Kim, Y. H., Yang, S. K., Jang, B. I., Cheon, J. H., Im, J. P., Kanai, T., Katsuno, T., Ishiguro, Y., Nagaoka, M., Isogawa, N., Li, Y., Banerjee, A., Ahmad, A., Hassan-Zahraee, M., Clare, R., Gorelick, K. J., Cataldi, F., ... Hibi, T. (2020). Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: The OPERA study. Intestinal Research, 18(1), 45-55. https://doi.org/10.5217/ir.2019.00039