Cilansetron: KC 9946.

Abstract

Cilansetron [KC 9946] is a serotonin-3 receptor (5-HT(3)) antagonist under development with Solvay Pharmaceuticals for the treatment of irritable bowel syndrome with diarrhoea predominance (IBS-D), in both men and women.5-HT(3) antagonists inhibit the 5-HT(3) receptors, resulting in decreased GI motility, secretion and sensation, thereby improving symptoms of IBS-D. Current 5-HT(3) therapy indicated for IBS-D is approved for women only.IBS is one of the most common functional gastrointestinal disorders, affecting an estimated 10-20% of the population in developed countries. Approximately twice as many women as men are diagnosed with IBS; however, this discrepancy may be due to more women seeking medical care. IBS is a chronic and bothersome disorder, and its symptoms, although not life-threatening, have a negative impact on quality of life (QOL), interfering with social activities, relationships and work. The degree to which IBS reduces quality of life appears to be directly related to symptom severity and intensity. In July 2001, Solvay signed an agreement with Quintiles (CRO) in order to optimise clinical research for cilansetron. In April 2004, Solvay Pharmaceuticals submitted a new drug application (NDA) for cilansetron in the UK (for the European Union) for the treatment of irritable bowel syndrome with diarrhoea predominance, in both men and women. In April 2005, Solvay Pharmaceuticals received a 'not-approvable' action letter from the US FDA on its NDA for cilansetron for the treatment of irritable bowel syndrome with diarrhoea predominance (IBS-D), in both men and women. The letter requested additional clinical trials, and Solvay is currently examining its options and will discuss future steps with the FDA. Solvay submitted the NDA for cilansetron in the US in June 2004 and included an extensive Appropriate Use Plan as part of its submission. The NDA submission was based on efficacy and safety studies in around 4000 patients worldwide with IBS-D. The FDA accepted for filing and granted priority review status for this NDA application in September 2004. According to Solvay's first half 2004 results, cilansetron is due to begin phase II clinical trials in Japan for the treatment of irritable bowel syndrome with diarrhoea predominance.