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ORLANDO -- The oral Smad7 antisense nucleotide mongersen alleviated both stool frequency and abdominal pain in patients with significant, longstanding Crohn's disease, according to research presented here.

In a cohort of 63 patients, clinical remission was achieved by 32% of patients receiving mongersen for 4 weeks, by 35% of those given the drug for 8 weeks, and by 48% of those treated for 12 weeks, reported Brian G. Feagan, MD, of Robarts Clinical Trials and the University of Western Ontario in Canada. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) below 150 and an abdominal pain score of 1 or lower, he explained during a poster session at the Advances in Inflammatory Bowel Diseases meeting.

Action Points Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The chronic intestinal inflammation characteristic of Crohn's disease is associated with an uncontrolled immune response to mucosal antigens in the gut and inadequate activity of transforming growth factor (TGF)-β1. Signaling of TGF-β1 is blocked by the intracellular protein Smad7, which is upregulated in Crohn's disease.

Mongersen is a delayed-release, pH-dependent formulation intended to be active only in the distal gastrointestinal tract, with little systemic activity.

To explore this agent's effects on endoscopic and clinical outcomes, adults with active disease, defined as a CDAI score of 220 or higher, were recruited from 23 sites. Participants had to have Simple Endoscopic Scores for CD (SES-CD) of 7 or higher, or at least 4 if their disease was limited to ileitis. They also were required to have failed (or been intolerant to) at least one other therapy, including aminosalicylates, budesonide, corticosteroids, immunosuppressants, or tumor necrosis factor (TNF) inhibitors.

The study randomized patients to receive 160 mg daily of mongersen for 4, 8, or 12 weeks, and an observational phase is planned for up to 52 weeks.

At baseline, patients' mean age was 42, slightly more than half were women, and duration of Crohn's disease was almost 12 years.

Almost half had previously been treated with TNF inhibitors, and one in four were taking corticosteroids.

The mean baseline CDAI score was 294, and mean SES-CD was 11.2. Mean daily abdominal pain score was 1.8 and daily stool frequency score was 5.4.

Improvements were seen as early as the second week in both abdominal pain and stool frequency scores, Feagan reported. Among patients receiving the drug for 4 weeks, abdominal pain scores were 1 or lower in 26% and stool frequency scores were 3 or lower. For those in the 8-week treatment group, 30% had those levels of improvement, as did 43% of those treated for 12 weeks.

Clinical benefits also were reported among patients with high disease activity at baseline, he noted. For example, among those whose endoscopic severity scores had been higher than 12, CDAI remission was seen in 30% by week 12, and in those who had previously received a TNF inhibitor, 24% reached remission. Among those who had both proximal and distal disease, 31% were in CDAI remission by week 12.

Also by week 12, there were decreases in CDAI scores of 100 points or more in 53% of those treated for 4 weeks, by 44% of those treated for 8 weeks, and by 67% of those treated for the full 12 weeks. In addition, reductions in SES-CD of 25% or more were seen in 37% of the entire cohort and in 63% of those whose baseline SES-CD was higher than 12.

Adverse events were similar in the three treatment groups, with most being likely related to their Crohn's disease. Serious adverse events were seen in 1% of each group, and there were no deaths.

"Oral mongersen resulted in meaningful endoscopic and clinical improvement at an early time point (12 weeks) for patients with active Crohn's disease," Feagan concluded.