Positive Ph IIb data for Microbio/Forest's linaclotide

Microbia and fellow USA-based Forest Laboratories have reported positive top-line results from two Phase IIb studies assessing the safety, efficacy and dose response of four different once-daily formulations of linaclotide: 75mcg, 150mcg, 300mcg and 600mcg. The first trial assessed linaclotide in subjects with chronic constipation, while the second examined its effects in patients with irritable bowel syndrome with constipation (IBS-C). Preliminary analysis of the CC study data and an interim analysis of the IBS-C trial findings indicate that each study met its primary endpoint, the firms noted.

In the four-week CC study, the primary efficacy endpoint was the change from pre-treatment in weekly spontaneous bowel movement frequency rate. Patients who received once-daily dosing of linaclotide demonstrated a dose-responsive increase in weekly SBM frequency rate ranging from 0.98 (75mcg, p = 0.09) to 2.99 (600mcg, p < 0.0001) compared to those on placebo. The response was significant at all doses above 75mcg. At this time, the companies have reviewed only top-line results and further analyses will be conducted in the coming weeks.

An interim analysis of a recently-completed 12-week IBS-C study was carried out to enable timely dose selection for Phase III trials, and was performed on the unlocked database following the last participant's last visit. IBS-C patients who received once-daily treatment with linaclotide experienced a significant increase in weekly CSBM frequency rate - the primary endpoint for this study - at all doses except for 150mcg. Linaclotide-treated patients also experienced improvements in all other top-line efficacy endpoints-SBM frequency, stool consistency, abdominal pain, bloating, abdominal discomfort, adequate relief and IBS-C symptom severity-that were statistically-significant for at least two of the four linaclotide dose groups for each endpoint, the companies added.