Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 26, Issue 8, Pages 991-997Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2017.1349753
Keywords
Inflammatory bowel disease; ulcerative colitis; anti-integrin; alicaforsen; safety; adverse events
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Introduction: Intracellular adhesion molecule-1 (ICAM-1), is a transmembrane glycoprotein of the immunoglobulin family, constitutively expressed on vascular endothelial cells and upregulated in inflamed colonic tissue. Alicaforsen, a 20 base ICAM-1 anti-sense oligonucleotide and highly selective ICAM-1 inhibitor, down-regulates ICAM-1 mRNA.Areas covered: We review mechanism of action, pharmacokinetics, pre-clinical, clinical and safety data of alicaforsen for the treatment of ulcerative colitis (UC), pouchitis and Crohn's disease (CD).Expert opinion: After 6weeks of treatment, topical alicaforsen was significantly more effective than placebo in inducing remission in patients with moderate-severe distal UC, with treatment effects lasting up to 30weeks. No difference was observed in head-head comparison with mesalamine topical enema, although alicaforsen appeared to have more durable treatment effect. Clinical trials of an intravenous formulation in Crohn's disease showed no significant treatment effect compared to placebo. An open-label trial in alicaforsen for pouchitis demonstrated encouraging results, now being assessed in a multi-national phase 3 trial. No major safety signals have been observed in UC patients treated with alicaforsen enemas. The potential as a novel therapy for pouchitis has led to orphan designation for this indication by the FDA and European Medicines Agency.
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