VIENNA – Fourteen days of daily treatment with mongersen, an oral, antisense oligonucleotide, safely produced remissions in two-thirds of patients with Crohn’s disease in a phase II study with a total of 163 patients.
The responses were also durable, with patients in remission continuing to show low disease activity at 10 weeks after they received their last dose of mongersen, Dr. Giovanni Monteleone reported at he United European Gastroenterology Global Congress.
The durability of patient response was not a surprise as similar findings occurred during phase I testing, he said. Mongensen “is not an anti-inflammatory drug. It removes a brake on the normal immunosupressant mechanism in the gut, and that is why the effect is long lasting. It allows TGF [transforming growth factor]-beta to work again [as an endogenous immunosuppressant] and promote healing,” said Dr. Monteleone, a professor of gastroenterology at the University of Rome Tor Vergata.
Mitchel L. Zoler/Frontline Medical News
Dr. Giovanni Monteleone
Dr. Silvio Danese, director of the IBD center at the Humanitis Research Hospital in Milan, said he was impressed by the frequent, durable, and apparently safe remissions achieved by mongensen treatment. “If the phase III studies show efficacy, mongersen will probably be a game changer” for treating inflammatory bowel disease, he commented.
Dr. Monteleone traced development on mongensen to work he published 13 years ago, which showed that oligonucleotide blockade of the production of the Smad7 intracellular protein prevented the inhibitory effect of Smad7 on TGF-beta and thus allowed TGF-beta to inhibit cytokine production and T lymphocyte signaling (J. Clin. Invest. 2001;108:601-9). His work also showed that patients with inflammatory bowel disease have elevated Smad7 levels in their intestinal mucosa, suggesting the potential for therapeutically cutting Smad7 levels in the gut of patients with inflammatory bowel disease.
The study he reported at the meeting included 163 patients with active Crohn’s disease at about a dozen hospitals in Italy. Patients had a Crohn’s disease activity index (CDAI) score of 221-400, were steroid dependent, steroid resistant, or both, and had documented lesions in their terminal ileum, right colon, or both. Patients randomized to active treatment received a daily pill for 14 days with one of three dosages of mongersen formulated into a tablet with a pH dependent coating designed to release the drug in the terminal ileum and right colon and avoid systemic absorption. The researchers then followed patients for an additional 70 days during which they received usual care but no additional treatment with mongersen or placebo.