Impact of patient characteristics on the clinical efficacy of mongersen (GED‐0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease

Abstract

SummaryBackgroundIn a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD).AimIn a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy.MethodsPatients with steroid‐dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C‐reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored.ResultsClinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated.ConclusionsPatients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C‐reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011‐002640‐27.)

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

“…Most adverse events were related to complications and symptoms of CD. This trial demonstrated a benefit in terms of the clinical remission rate, as well as the safety and tolerability, of Mongersen in active CD patients [87]. Further studies involving a large population of CD patients are needed to confirm the safety and efficacy of Mongersen.…”

“…In a phase I trial of Mongersen, 15 patients with active CD received one of three doses of Mongersen (40, 80, or 160 mg), and the results demonstrated its safety and tolerability [86]. In a phase II trial, 166 patients with active CD were randomly assigned to receive one of three doses of Mongersen (10, 40, or 160 mg) or placebo [85,87]. The primary outcome of this phase II trial, which was the clinical remission rate at day 15 of Mongersen treatment, was achieved in 55 and 65% of patients in the 40 and 160 mg Mongersen groups, respectively, compared with 10% for the placebo group.…”

New and Evolving Immunotherapy in Inflammatory Bowel Disease

“…A phase II trial involved 166 patients randomized to 10, 40, or 160 mg/day of mongersen or placebo for 2 weeks with clinical assessments done at 2, 4, and 12 weeks. Both clinical remission and response rates were significantly higher in patients receiving a 40 or 160 mg/day regimen than in patients receiving placebo at all 3 time points irrespective of disease duration or C-reactive protein (CRP) level [57]. After adjusting for baseline Crohn's Disease Activity Index (CDAI) scores in a logistic regression at week 4, the CDAI score was found to be the only factor affecting the likelihood of clinical remission or response.…”

Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease

“…Therefore, it is possible that the remission assessed by clinical and endoscopic evaluation was incomplete in these cases. Thus, a clinical relapse is typically assessed based on the clinical activity index (CAI) (17), or the Crohn's Disease Activity Index (CDAI) (18), rather than on the endoscopic findings. The present study analyzed the gene expression profiles of inflamed and unaffected colon mucosa from patients with mild CD and UC, in order to establish a more sensitive method for monitoring mucosal impairment.…”