Sucampo and Takeda Report Negative Results in One of Two Phase III Trials with Bowel Dysfunction Drug

Sucampo Pharmaceuticals and Takeda Pharmaceutical reported that one of two identical Phase III studies assessing lubiprostone as a treatment for opioid-induced bowel dysfunction failed to meet its primary endpoint. Additionally, a particularly high response rate among placebo-treated patients was observed.

The two North American Phase III trials, OBD0631 and OBD0632, were assessing lubiprostone in opioid-treated patients with chronic, noncancer pain. The companies confirmed that they will continue with the ongoing, open-label safety trial, OBD0631, assessing lubiprostone in patients with chronic, noncancer pain, which is due to report in late 2009. If this trial is successful, data will be submitted to FDA in 2010.

Trials 631 and 632 included a total of 875 patients receiving opioid therapies. Participants received either placebo or lubiprostone twice-daily for 12 weeks in addition to their opioid medications, which included morphine, methadone, oxycontin, or fentanyl.

While trial 631 met its primary endpoint (a statistically significant change from baseline in the frequency of spontaneous bowel movements at week eight of treatment) and eight of 12 secondary endpoints including key symptoms associated with OBD, trial 632 failed to meet its primary endpoint and met only two of its secondary endpoints; positive trends were achieved in another four. In this trial some 58% of subjects treated with placebo experienced more than three spontaneous bowel movements (SBMs) a week.  The overall adverse event rate for the combined trials was 54.9% for lubiprostone and 51.6% for placebo.

Lubiprostone, whic his marketed as Amitiza, is a local activator of type 2 chloride channels in cells lining the small intestine, which acts to increase fluid secretion into the intestinal tract. The drug was approved in the U.S. for the treatment of adult chronic idiopathic constipation (CIC) in 2006 and in 2008 for treating irritable bowel syndrome with constipation in women aged 18 years and older. The drug is co-marketed in the U.S. by Sucampo and Takeda’s U.S. businesses. Marketing submissions have been made in a number of EU countries.

In February 2009, Sucampo entered into a license, commercialization, and supply agreement with Abbott Laboratories covering the use of Amitiza in Japan for the CIC indication. It gives Abbott the right of first refusal for future indications. Clinical development of the drug in Japan is ongoing.

Sucampo reported yearly increases in product royalty revenues since Amitiza’s first market introduction, which reached $34.4 million in 2008. These were based on net U.S. sales of $193 million, as reported by Takeda in 2008, up from $155 million i n 2007.