Sunday, April 12, 2015
Antisense Drug Highly Effective Against Crohn's Disease
Mongersen, a drug that restores transforming growth factor β1 (TGF-β1) signaling, is highly effective, according to the results of a randomized controlled trial published in the March 19 issue of the New England Journal of Medicine. The data also suggest the experimental drug has longer-lasting effects in patients with Crohn's disease than existing anti–tumor necrosis factor α therapy.
Anti– tumor necrosis factor α drugs (infliximab and adalimumab) have been used for almost 20 years, but they have not significantly reduced disease progression or surgical rates, perhaps because they are used in advanced disease. A parallel therapeutic trajectory targets TGF-β1, which normally regulates the immune response against pathogenic microorganisms in the ileum and colon.
Giovanni Monteleone, MD, PhD, from the Department of Systems Medicine at the Università Tor Vergata in Rome, Italy, and colleagues conducted a double-blind, randomized, placebo-controlled dose escalation phase 2 clinical trial of mongersen. The drug is a 21-base single-stranded oligonucleotide that binds (is antisense to) the messenger RNA of SMAD7, a protein that too readily binds the TGF-β1 receptor in Crohn's disease, inflaming the mucosa. Mongersen is a proprietary modified-release tablet that delivers the drug to the lumen of the terminal ileum and right colon.