The legions of individuals who suffer from chronic idiopathic constipation or constipation-predominant irritable bowel syndrome (IBS-C) may soon have another therapy with which to address their discomfort. Ironwood Pharmaceuticals and its partners, Forest Laboratories and Almirall are developing linaclotide. It is an oral peptide that acts through GCC receptors in the intestinal tract — the same receptors activated by the bacterial toxins implicated in E coli diarrhea. Via this unique mechanism, linaclotide increases intestinal fluid secretion, thereby relieving constipation.

The companies have reported positive results for two phase III chronic constipation trials. The two pivotal phase III trials in IBS-C should complete soon and results should be released in Q4. The data so far are fairly encouraging, however there are some key questions. For example, are available results clinically relevant even if statistically significant? Does the program meet new standards for IBS therapies that FDA has just released? Will there be overhang from FDA’s experience with other IBS therapies withdrawn from the market due to postmarketing safety issues (think Zelnorm)? And most important, how will linaclotide fare in the marketplace against Amitiza? Check our latest report for an in-depth discussion of these questions.