Ironwood Pharmaceuticals, Inc. and Forest Laboratories, Inc. announced they have recently submitted a New Drug Application (NDA) to the US Food and Drug Administration (US FDA) for linaclotide, a guanylate cyclase type-C (GC-C) agonist, for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC).
The submission includes efficacy and safety data from a phase III programme comprising four double-blind placebo-controlled trials and two open-label long term safety studies. A total of more than 2,800 patients received a once-daily dose of either linaclotide or placebo across the four placebo-controlled clinical trials: two trials in patients with IBS-C and two trials in patients with CC. In these trials, statistically significant improvements in abdominal and bowel symptoms were achieved for linaclotide-treated patients versus placebo-treated patients for all primary and secondary endpoints.
Safety data collected across the four placebo-controlled phase III clinical trials demonstrated that diarrhoea was the most commonly reported adverse event and led to study discontinuation in 4 per cent to 5 per cent of linaclotide-treated patients compared to fewer than 1 per cent of patients receiving placebo. Additionally, over 3,200 patients have enrolled in ongoing open-label safety studies and more than 1,100 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. It 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. Ironwood and Forest plan to co-promote linaclotide in the United States. Ironwood has out-licensed linaclotide to Almirall, SA 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. It can have an impact on daily living. There are currently few available therapies to treat this disorder.
As many as 34 million Americans suffer from symptoms associated with CC and 8.5 million patients have sought treatment. Patients with 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. There is a high rate of dissatisfaction with currently available treatments for CC.
Ironwood Pharmaceuticals is an entrepreneurial pharmaceutical company dedicated to the art and science of great drug making.
Forest Laboratories’ long standing 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.