Lubiprostone: RU 0211, SPI 0211

Lubiprostone [RU 0211, SPI 0211] is a bicyclic fatty acid that acts as a chloride channel opener, increasing intestinal water secretion. Lubiprostone, an orally-administered formulation, is one of a series of functional fatty acid compounds discovered by Dr Ryuji Ueno, and is currently undergoing development for the treatment of constipation, constipation-predominant irritable bowel syndrome (IBS-C) and postoperative ileus with Sucampo Pharmaceutical's. Lubiprostone activates a specific chloride channel (CLC2) on cells lining the gut, thereby naturally increasing intestinal fluid secretion. The increased fluid level softens the stool, promotes spontaneous bowel movements, and reduces abdominal discomfort/pain and bloating. The chloride channel is a protein that controls cell membrane transport of chloride ion. Lubiprostone acts on the ClC-2 chloride channel, which is located in the apical intestinal membrane. In November 2004, Takeda Pharmaceuticals entered into a collaboration and licensing agreement for Lubiprostone with Sucampo Pharmaceuticals for the treatment of chronic constipation and constipation-predominant Irritable Bowel Syndrome (c-IBS). Under the terms of the agreement, Takeda received the right to market the product in the US and Canada, while Sucampo reserved the co-promotion rights for these countries. Takeda's wholly-owned US subsidiary, Takeda Pharmaceuticals North America Inc., will sell lubiprostone once the product is approved by the US FDA. Takeda will also receive an option for marketing rights in other territories, including Japan and Europe. Takeda and Sucampo agreed on the exclusive manufacturing and supply of Lubiprostone by R-Tech Ueno, Ltd, a member of the Sucampo Group. Sucampo has the potential to receive up to dollar US 210 million in initial and milestone payments, some of which are contingent upon the successful achievement of several milestones. Takeda will fund a major part of development costs not only for chronic constipation and c-IBS, but also for other indications in the gastroenterology field. Takeda will make royalty payments to Sucampo after the product is launched. In May 2005, Sucampo received dollar US 20 million from Takeda Pharmaceutical as payment for achieving a development milestone of initiating a phase III clinical trial of lubiprostone to treat patients with constipation-predominant irritable bowel syndrome. Sucampo Pharmaceuticals submitted a new drug application (NDA) for lubiprostone to the FDA on 31 March 2005 for approval in the treatment of chronic idiopathic constipation (CIC) and associated symptoms in adults. Sucampo completed three long-term, open-label safety studies, which will support the NDA for lubiprostone, in treating constipation. Results from its second open-label safety study with lubiprostone were announced in February 2004, with the first two studies demonstrating long-term safety and sustained effectiveness in constipated subjects. In the US, the final phase III study for chronic constipation was completed in the fourth quarter of 2004. In November 2004, Sucampo announced completing a phase II safety and efficacy study of lubiprostone for the treatment of IBS-C. This study, which was initiated in April 2003, randomised 195 patients with documented IBS into four treatment groups (three doses of SPI 0211 and placebo) from 19 locations throughout the US.