Atlantic Healthcare announced the results of a Phase 3 trial of Camligo (alicaforsen enema) for the treatment of pouchitis. The trial did not meet its co-primary endpoints, which were the proportion of patients achieving endoscopic remission and a reduction in stool frequency at week 10. Secondary endpoints assessed improvement in Quality of Life.
The multi-center, double-blind randomized controlled phase 3 trial enrolled 138 patients with chronic antibiotic refractory pouchitis (failed to adequately respond to one or more courses of antibiotics) at 40 centers across the U.S., Canada and Europe. Patients received Camligo 240mg once daily for six weeks, or a placebo. In the primary analysis, using an adaptation of the Mayo Score of improvement in endoscopic remission and bowel frequency, the trial did not meet its co-primary endpoints. However, the data for stool frequency do show an encouraging efficacy signal and remission in 34% of patients. In addition, a re-evaluation of the endoscopy data, using new methods of analysis, indicates a statistically significant endoscopic response was achieved in several subgroups of patients.
Based on this data, Atlantic Healthcare intends to meet with the U.S. Food and Drug Administration and European Medicines Agency to discuss a pathway to regulatory approval.
Pouchitis is estimated to impact the lives of approximately 200,000 patients in the U.S. and Europe. It is a progressive disease characterized by inflammation, ulceration and increasingly uncontrolled, frequent and urgent emptying of the bowel (up to 10-20 times a day and night).
Alicaforsen is an antisense oligonucleotide targeted to down regulate the production of ICAM-1, a cell surface receptor which is involved in the process of inflammation. In inflammatory bowel disease (IBD), the immune system incorrectly activates inflammatory processes. Part of this activation involves increasing the levels of gene messengers (mRNA) for the production of ICAM-1; there is a correlation between the levels of ICAM-1 and the severity of inflammation. ICAM-1 facilitates the transport of white cells from the circulation to the site of inflammation, thereby propagating the inflammatory condition. When alicaforsen binds to ICAM-1 mRNA, ICAM-1 expression is reduced.