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

Journal article

Publication Details

Author(s): Monteleone G, Neurath M, Ardizzone S, Di Sabatino A, Fantini MC, Castiglione F, Scribano ML, Armuzzi A, Caprioli F, Sturniolo GC, Rogai F, Vecchi M, Atreya R, Bossa F, Onali S, Fichera M, Corazza GR, Biancone L, Savarino V, Pica R, Orlando A, Pallone F
Journal: New England Journal of Medicine
Publication year: 2015
Volume: 372
Journal issue: 12
Pages range: 1104-13
ISSN: 0028-4793


Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor ?1 (TGF-?1) due to high levels of SMAD7, an inhibitor of TGF-?1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.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.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<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease.We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).

FAU Authors / FAU Editors

Atreya, Raja Prof. Dr.
Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur)
Neurath, Markus Prof. Dr.
Lehrstuhl für Innere Medizin I

External institutions with authors

Azienda ospedaliera San Camillo-Forlanini
Careggi University Hospital / Azienda Ospedaliero Universitaria Careggi
Catholic University of the Sacred Heart / Università Cattolica del Sacro Cuore
Istituto di ricovero e cura a carattere scientifico (IRCCS)
Luigi Sacco Hospital
Sandro Pertini Hospital / Ospedale Sandro Pertini
Università degli studi di Milano
Università degli Studi di Napoli Federico II
Università degli Studi di Palermo
Università degli Studi di Pavia
Università degli Studi di Roma 'Tor Vergata'
University of Genova / Università degli Studi di Genova
University of Padua / Universita degli Studi di Padova

How to cite

Monteleone, G., Neurath, M., Ardizzone, S., Di Sabatino, A., Fantini, M.C., Castiglione, F.,... Pallone, F. (2015). Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. New England Journal of Medicine, 372(12), 1104-13.

Monteleone, Giovanni, et al. "Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease." New England Journal of Medicine 372.12 (2015): 1104-13.


Last updated on 2018-09-10 at 02:26