Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohn’s Disease

 

Giovanni Monteleone, M.D., Ph.D. University Tor Vergata, Rome, Italy

 

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

N Engl J Med 2015; 372:1104-1113; March 19, 2015DOI: 10.1056/NEJMoa1407250

 

This was a phase 2, randomized, double-blind, placebo-controlled trial aimed at evaluating the clinical efficacy of Mongersen in patients with active, steroid-dependent/resistant Crohn’s disease. Mongersen is an oral antisense oligonucleotide that targets Smad7, an inhibitor of the immunosuppressive cytokine transforming growth factor-b1. Patients were randomly assigned to receive 10, 40 or 160 mg/day Mongersen or placebo for 2 weeks. The proportions of patients who reached clinical remission, defined by a Crohn’s disease activity index (CDAI) score of less than 150 at day 15 which was maintained for at least 2 weeks, were 55.0% and 65.1% for 40 and 160 mg of Mongersen, respectively, as compared with 12.2% and 9.5% for 10 mg/day Mongersen and placebo, respectively. The clinical efficacy of the drug was confirmed in subgroups of patients with high C-reactive protein at baseline and at the end of follow-up (day 84) more patients treated  with the highest dose of the drug discontinued steroids as compared to the placebo group. The rate of clinical response (reduction of CDAI score of 100 points at day 28) was significantly greater among patients receiving 10 (36.6%), 40 (57.5%) or 160 mg (72.1%) Mongersen respectively than that documented in the placebo group (16.7%). The occurrence of serious adverse events and adverse events did not significantly differ among groups. Overall these data indicate that induction therapy with Mongersen for Crohn’s disease was safe and resulted in significantly high rates of clinical remission and response.

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