Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease

Giovanni Monteleone, Markus F. Neurath, Sandro Ardizzone, Antonio Di Sabatino, Massimo C. Fantini, Fabiana Castiglione, Maria L. Scribano, Alessandro Armuzzi, Flavio Caprioli, Giacomo C. Sturniolo, Francesca Rogai, Maurizio Vecchi, Raja Atreya, Fabrizio Bossa, Sara Onali, Maria Fichera, Gino R. Corazza, Livia Biancone, Vincenzo Savarino, Roberta PicaAmbrogio Orlando, Francesco Pallone

Research output: Contribution to journalArticle

Abstract

Background Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. Methods In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. Results The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P

Original languageEnglish
Pages (from-to)1104-1113
Number of pages10
JournalNew England Journal of Medicine
Volume372
Issue number12
DOIs
Publication statusPublished - Mar 19 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Monteleone, G., Neurath, M. F., Ardizzone, S., Di Sabatino, A., Fantini, M. C., Castiglione, F., Scribano, M. L., Armuzzi, A., Caprioli, F., Sturniolo, G. C., Rogai, F., Vecchi, M., Atreya, R., Bossa, F., Onali, S., Fichera, M., Corazza, G. R., Biancone, L., Savarino, V., ... Pallone, F. (2015). Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease. New England Journal of Medicine, 372(12), 1104-1113. https://doi.org/10.1056/NEJMoa1407250