Crohn's disease - alicaforsen
Crohn's disease is an unpleasant condition in which sections of the intestinal tract become inflamed, thickened and ulcerated. In its chronic form, it can cause the partial obstruction of the intestine, giving pain, diarrhoea and leading to food not being properly absorbed.
Alicaforsen, formerly known as ISIS 2302, is a new medication being developed to treat Crohn's disease by Isis Pharmaceuticals. It is an intercellular adhesion molecule-1 (ICAM-1) antisense phosphorothioate oligonucleotide.
Cellular adhesion molecules are found on the surface of most cells within the body, including those that line the gastrointestinal tract. They play a vital role in numerous functions in the body, including tissue development and maintenance, movement of immune and inflammatory cells to sites of inflammation, initiation and transmission of immune responses, and wound healing.
ICAM-1 is involved in the production of immune factors that cause the inflammatory response in Crohn's disease.
Twenty patients with active, steroid treated Crohn's disease were randomly given saline placebo, or 0.5, 1 or 2 mg/kg alicaforsen every other day for 26 days in a double blinded study.1 After the treatment, 7 of the 15 given active and one given placebo were in remission, and after six months, five of the treated patients were still in remission.
In another trial, 299 patients with steroid dependent Crohn's disease were randomised to receive placebo or 2 mg/kg alicaforsen for two or four weeks.2 Patients were treated in months one and three, with steroid withdrawal attempted by week 10. At week 14, steroid withdrawal was successful in 78% of treated patients, compared with 64% of those given placebo.
In a further, open label, trial in 22 patients, subjects were given 4-5mg/kg three times a week for four weeks by intravenous infusion.3 These doses were about two and a half times higher than those previously investigated. Patients who responded to treatment were followed for six to twelve months, and all patients remained on their other anti-Crohn's medications, other than infliximab. A total of 13 of the 17 evaluable patients achieved a response, and nine experienced clinical remission. Five of these were also steroid and immunosuppressant free after treatment.
Alicaforsen is now undergoing Phase III trials to establish its usefulness as a treatment for Crohn's disease at higher doses. The product is also being evaluated as a potential treatment for the related condition ulcerative colitis, and also as a topical treatment for psoriasis.