Gastroenterology

Among the most advanced research projects, dexloxiglumide (CR 2017) is a cholecystokinin (CCK)-1 receptor antagonist. Interaction of CCK with the CCK-1 receptor at the level of the digestive system controls some secretory functions and, especially visceral motility and sensory pathways. Rottapharm recently released highly favourable preliminary results of a large Phase III European clinical trial (the DARWIN study) in patients with constipation-predominant Irritable Bowel Syndrome (IBS). The data are under discussion with the FDA and the EMEA to arrange the next steps towards possible product approval.
Assessment of the efficacy of dexloxiglumide in other functional bowel disorders, including Functional Dyspepsia and GastroEsophageal Reflux Disease (GERD), is also ongoing.

Itriglumide (CR 2945) is a selective antagonist of the CCK-2 receptor, which plays a regulatory role at both the gastrointestinal and Central Nervous System (CNS) levels. In the GI tract, CCK-2 receptors are contributing to the control of gastric acid secretion, but they may have a regulatory role in visceral motility and sensitivity as well. In addition, they control mucosal growth at the level of different organs. Use of itriglumide for its peripheral gastrointestinal effects might therefore optimise antisecretory therapy in GERD and be used in functional GI disorders with an acid-related component, such as some of the variants of Functional Dyspepsia. Several preclinical studies indicate that itriglumide might also be beneficial for the treatment of gastrointestinal neoplasms .The compound is undergoing Phase II clinical trials.

CR3294 is an inhibitor of pro-inflammatory gene expression, with potent reactive-oxygen-species (ROS)- generation preventing effect, endowed with strong preventive effect of GI mucositis induced by chemotherapy and/or radiotherapy in animal experimental models. Two phase 1 clinical studies have been completed and Phase II trials will start in the second quarter of 2010.

Among line extensions of existing products, it is worth noting the current developments on silibinin. Silibinin is one of the main component of the flavonolignans in sylimarin, the active ingredient of the Rottapharm | Madaus product Legalon®. The compound has been recently shown to be an inhibitor of the RNA polymerase of the hepatitis C virus (HCV) and to have potent anti-viral effects in HCV patients that were non-responders to standard anti-viral therapy.