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New Drug for Crohn's Disease Shows Early Promise

Mongersen achieves higher remission rates versus placebo in mid-stage trial

An experimental treatment may be able to quickly quash the symptoms of Crohn's disease — at least for the short term, an early clinical trial finds.

According to the study’s authors, the bowel inflammation associated with Crohn’s disease is linked to reduced activity of an immunosuppressive cytokine, transforming growth factor (TGF) beta-1, due to high levels of SMAD7, an inhibitor of TGF beta-1 signaling. Preclinical studies and a phase I trial have shown that mongersen, an oral SMAD7 antisense oligonucleotide, targets ileal and colonic SMAD7.

In a phase II, double-blind, placebo-controlled study, researchers in Italy evaluated the efficacy of mongersen in 166 patients with active Crohn’s disease. The patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo each day for 2 weeks. The study’s primary endpoint was 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. A secondary outcome was the clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28.

The primary endpoint was reached by 55% and 65% of the 40-mg and 160-mg mongersen groups, respectively, compared with 10% of the placebo group (P < 0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P = 0.04, P < 0.001, and P < 0.001, respectively).

Most adverse events were related to the complications and symptoms of Crohn’s disease rather than to the active treatment, the authors reported.

Current therapies for Crohn’s disease can have adverse effects, including infections and other immune-related diseases, such as psoriasis, lead researcher Dr. Giovanni Monteleone told HealthDay.

The advantage of mongersen is that it’s taken orally, which allows “maximal release” of the active compound to inflamed sites in the digestive tract, Monteleone said. The drug works by restoring the natural activity of the anti-inflammatory TGF beta-1 protein, he explained.

Dr. Raymond Cross, a gastroenterologist at the University of Maryland Medical Center, who was not involved in the study, described the results as “impressive.” He added, however, that “you can’t really assess safety in two weeks.”

Sources: Medical Xpress; March 19, 2015; and NEJM; March 19, 2015.

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