As many as one in five Americans, or 55 million people, suffer with the abdominal discomfort associated with irritable bowel syndrome (IBS), according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Symptoms vary from patient to patient but typically include abdominal pain and discomfort with changes in bowel function-either predominantly diarrhea (IBS-d) or constipation (IBS-c). Some patients, however, experience a mixed form (IBS-m), with alternating diarrhea and constipation. Currently there exist few therapies for treating the condition; however, several entities in development look promising.
In phase II, renzapride led to a 25% improvement in relief of overall IBS symptoms, compared with placebo, when tested in patients with IBS-c. Renzapride increased the frequency of bowel movements for patients with constipation and improved stool consistency. The drug was also tested in 168 patients in Europe with IBS-m. In a small phase II trial of 48 patients with IBS-c at the Mayo Clinic, renzapride was associated with an improvement in bowel function scores and accelerated colonic transit, although gastric emptying and small bowel transit were not affected. Currently, the drug is being evaluated in a phase III trial for safety and efficacy in 1,700 females with IBS-c. Results are expected in the second half of 2007, according to the manufacturer.
Asimadoline is also being studied in phase IIa for postoperative ileus to evaluate its usefulness in improving recovery time in patients undergoing laparoscopic segmental colonic resections.
In a phase II trial of 141 patients, both males and females with IBS-d and IBS-m were randomized to 12 weeks of treatment with 200 mg of dextofisopam, given twice daily, or placebo. For the primary endpoint of overall relief of IBS symptoms, patients taking dextofisopam reported adequate relief 57% of the time, whereas patients taking placebo reported relief 43% of the time. The positive effect of treatment was more evident during the first month of therapy, with a 25% superiority of dextofisopam over placebo. Dextofisopam provided adequate relief more often than placebo in both men and women and in both the IBS-d and IBS-m patients.
In September 2006, Pharmos Corp. announced it had signed an agreement for the acquisition of Vela Pharmaceuticals. As part of the deal, Pharmos will pay Vela $1 million upon enrollment into dextofisopam's phase IIb trial and another $1 million upon enrollment of the final patient. Upon successful completion of the trial, Pharmos will pay $2 million and issue 2.25 million shares of common stock. At the closing of the acquisition, Pharmos said it will commence a dose-ranging study in women with IBS-d and IBS-m in 480 patients at 80 sites in the United States. The study is expected to begin sometime in early 2007.