The US Food and Drug Administration (FDA) has notified to Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc.  that it will require a three-month extension to complete its review of the data supporting the New Drug Application (NDA) for linaclotide for the treatment of irritable bowel syndrome with constipation (IBS-C).

An additional analysis of existing data was recently requested by the FDA to further characterize the relative effect of the two doses of linaclotide that were studied in the phase III CC clinical trials.

Since this analysis was submitted to the FDA within three months of the user fee goal date, the date has been extended by three months, in accordance with applicable regulation. No new data have been requested by the agency to complete the review. FDA action is now expected by September 2012. Ironwood and Forest continue to plan for a 2012 launch.

The efficacy and safety of linaclotide was studied in a clinical trial program of more than 2,800 patients for the treatment of IBS-C and CC. Additionally, over 3,200 patients were enrolled in ongoing open-label safety trials and more than 2,000 of those patients have received linaclotide for at least 12 months.

Linaclotide, an investigational drug, is an agonist of the guanylate cyclase type-C (GC-C) receptor located on the luminal surface of the intestine. In preclinical models, linaclotide reduced visceral hypersensitivity, increased fluid secretion, and accelerated intestinal transit. The effects on secretion and transit are mediated through cyclic guanosine monophosphate (cGMP), which is also believed to modulate the activity of local nerves to reduce pain.

Linaclotide is an orally delivered peptide that acts locally in the gut with no measurable systemic exposure at therapeutic doses and is intended for once-daily administration. An issued composition of matter patent for linaclotide provides protection to 2025 in the United States. Ironwood and Forest plan to co-promote linaclotide in the U.S. Ironwood has out-licensed linaclotide to Almirall for European development and commercialization, and to Astellas Pharma Inc. for development and commercialization in Japan, Indonesia, Korea, the Philippines, Taiwan, and Thailand.

IBS-C is a chronic functional gastrointestinal disorder characterized by abdominal pain, abdominal discomfort, and bloating associated with altered bowel habits, and as many as 11 million people in the US suffer from it. IBS-C can have a negative impact on daily living. There are currently few available therapies to treat this disorder.

Patients with Chronic Constipation (CC) often experience hard and lumpy stools, straining during defecation, a sensation of incomplete evacuation, and fewer than three bowel movements per week, as well as abdominal discomfort and bloating.

Ironwood Pharmaceuticals is an entrepreneurial pharmaceutical company dedicated to the art and science of great drug making. Linaclotide, Ironwood’s GC-C agonist, is an investigational drug for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC).

Forest Laboratories’ longstanding global partnerships and track record developing and marketing pharmaceutical products in the United States have yielded its well-established central nervous system and cardiovascular franchises and innovations in anti-infective and respiratory medicine.