Celgene Corporation recently presented data on a phase II trial of GED-0301 (mongersen) in patients with active Crohn’s disease at the Digestive Disease Week (DDW) held in Washington, D.C., May 16 to 19, 2015. The primary findings of this phase II trial were published this March on the The New England Journal of Medicine, under the title “Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohn’s Disease.”
Crohn’s disease is a chronic inflammatory condition of the digestive tract that can cause fever, fatigue, abdominal pain, diarrhea, malnutrition and weight loss. It is estimated to affect 3 in every 1,000 individuals in North America and Europe. There is no cure for Crohn’s disease and its exact cause is unknown.
Patients with Crohn’s disease usually have abnormally high levels of a protein called Smad7, which is known to be able to block the activity of the immunosuppressive cytokine transforming growth factor (TGF)-beta 1 in the gut, causing an increased inflammation. GED-0301 is an experimental oral therapy based on an oligonucleotide (a short nucleic acid molecule) that targets Smad7 reducing its protein levels.
Celgene’s GED-0301 phase II trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 166 adult patients with active Crohn’s disease, which was defined as a Crohn’s Disease Activity Index (CDAI) score higher than 220 and lower or equal to 400. Patients were treated with GED-0301 (10, 40 or 160 mg tablets, once daily) or a placebo drug for two weeks and followed-up for ten weeks. Celgene’s presentation at DDW retrospectively analyzed certain subgroups of patients enrolled in the trial.
“For patients with Crohn’s, disease severity and duration can influence the therapeutic effect of certain medicines,” said in a news release Dr. Giovanni Monteleone from the University of Rome Tor Vergata. “This subgroup analysis of data from the phase II study explored the effects of these factors on clinical response and clinical remission rates with GED-0301”
Patients were divided according to their disease duration (less than 5 years, or 5 years or more), baseline CDAI score (less than 260, or 260 or higher) and baseline levels of the C-reactive protein (CRP), an inflammatory marker (less than 3 mg/L, or 3 mg/L or higher). Researchers then assessed clinical remission (CDAI score lower than150) and clinical response (CDAI score reduction of 100 points or more from the baseline score) two and four weeks after treatment.
Researchers found that patients treated with 160 mg of GED-0301 had higher clinical remission rates (62.5 – 75%) than patients in the placebo group (5 – 24%). The clinical remission rates in patients treated with 160 mg GED-0301 were similar irrespective of their disease duration, baseline CDAI or CRP levels.
In terms of safety, the percentage of patients who reported having at least one adverse event was found to be slightly lower in patients under GED-0301 treatment (49 to 62%) than in the placebo group (67%). Serious adverse events were similar between the GED-0301 160 mg groups and the placebo group (2%). The most common adverse events reported in the GED-0301 treatment groups were Crohn’s disease worsening, urinary tract infection, abdominal pain and CRP increase.
“The analysis presented at DDW suggests that patients with more severe Crohn’s disease or a longer duration of disease were able to achieve clinical response or clinical remission with the 160 mg dose of GED-0301,” concluded the President of Celgene Inflammation and Immunology, Scott Smith. “Patients with moderate to severe Crohn’s disease are in need of new treatment options. Based on these findings, and as part of our commitment to bringing innovative medicines to this patient community, we look forward to continued study of this potentially transformative therapy in phase III trials.”