Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohn’s Disease
Giovanni Monteleone,Markus F. Neurath,Sandro Ardizzone,Antonio Di Sabatino,Massimo Fantini,Fabiana Castiglione,Maria Lia Scribano,Alessandro Armuzzi,Flavio Caprioli,Giacomo Carlo Sturniolo,Francesca Rogai,Maurizio Vecchi,Raja Atreya,Fabrizio Bossa,Sara Onali,Maria Fichera,Gino Roberto Corazza,Livia Biancone,Vincenzo Savarino,Roberta Pica,Ambrogio Orlando,Francesco Pallone +21 more
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TLDR
It was 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.Abstract:
BackgroundCrohn’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. MethodsIn 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. ResultsThe proportions of patients who reached the prim...read more
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