Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) announced today that dosing has begun in its Phase IIa clinical study of its investigational compound IW-3718 in patients suffering from gastroesophageal reflux disease (GERD) who have not responded adequately to treatment with a proton pump inhibitor (PPI). Data are expected in the first half of 2015.
“There are an estimated 7 million patients in the U.S. who suffer regularly from symptoms of GERD – such as heartburn and regurgitation – despite receiving the current standard of care of treatment with a proton pump inhibitor to suppress stomach acid production. For many of these refractory GERD patients, research suggests reflux of bile acid from the intestine into the stomach and esophagus may play an important role in their ongoing suffering,” said Michael Hall, MB. BCh., senior vice president, clinical development of Ironwood. “Refractory GERD is a significant unmet need among those suffering with gastrointestinal disorders, and we are investigating IW-3718 to assess whether it may help prevent bile acid reflux and provide relief for patients.”
Preliminary findings from non-clinical studies conducted by Ironwood and collaborators have shown that bile acids can cause relaxation (opening) of the lower esophageal sphincter, which allows reflux of contents from the stomach into the esophagus. Bile and bile acids were also shown to cause increased activity of esophageal nerve fibers in related non-clinical studies. Importantly, these study data suggest that a bile acid sequestrant may be able to block these actions. Collectively, these and other data provide additional evidence to suggest that bile acids could play a role in the pathophysiology of refractory GERD, and that a targeted bile acid sequestrant could have therapeutic utility in the treatment of this disorder.
IW-3718 is a novel gastric retention formulation of a bile acid sequestrant, created by Ironwood, and co-developed with Depomed Inc. through incorporation of its proprietary Acuform® drug delivery technology. IW-3718 is designed to deliver the bile acid sequestrant to the desired sites of action – specifically the stomach and duodenum (upper small intestine) – over an extended period of time. Data from non-clinical studies support the extended release profile of IW-3718.