Intracellular adhesion molecule-1 (ICAM-1) is a key protein involved in inflammation, particularly in the colon. Alicaforsen, a 20 base ICAM-1 anti-sense oligonucleotide, effectively down-regulates ICAM-1 mRNA, offering a targeted approach to treating inflammatory bowel diseases (IBD) such as ulcerative colitis (UC), pouchitis, and Crohn's disease (CD).
Clinical trials have shown that after 6 weeks of treatment, topical alicaforsen significantly outperformed placebo in inducing remission in patients with moderate-severe distal UC, with effects lasting up to 30 weeks. Although no significant difference was observed in a head-to-head comparison with mesalamine topical enema, alicaforsen demonstrated a more durable treatment effect. However, intravenous formulations of alicaforsen did not show a significant treatment effect in Crohn's disease compared to placebo.
An open-label trial for alicaforsen in treating pouchitis has yielded encouraging results, leading to its evaluation in a multi-national phase 3 trial. The safety profile of alicaforsen enemas in UC patients has been favorable, with no major safety signals reported. Recognizing its potential as a novel therapy for pouchitis, the FDA and European Medicines Agency have granted alicaforsen orphan designation for this indication.
