Ironwood Pharmaceuticals, Inc., an entrepreneurial pharmaceutical company dedicated to the art and science of great drugmaking, and New York-based Forest Laboratories, Inc. have received the US Food and Drug Administration (FDA) approval for Linzess (linaclotide) as a once-daily treatment for adult men and women suffering from irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). IBS-C and CIC are chronic functional gastrointestinal disorders affecting millions of people.
Symptoms associated with IBS-C include abdominal pain and constipation; symptoms associated with CIC include constipation (infrequent stools, hard stools and incomplete evacuation). There are few treatment options for these conditions, particularly options that relieve abdominal pain associated with IBS-C.
“The symptoms experienced by patients with IBS-C and chronic idiopathic constipation can have a significant impact on affected individuals,” said William D Chey, MD, professor of gastroenterology at the University of Michigan Health System. “The approval of Linzess provides physicians with a new, evidence-based, effective treatment option for their adult patients with IBS-C and chronic idiopathic constipation.”
Linaclotide, the active ingredient in Linzess, is a first-in-class guanylate cyclase-C (GC-C) agonist and acts locally in the intestine with minimal systemic exposure. In non-clinical studies, linaclotide has been shown to reduce intestinal pain and accelerate gastrointestinal transit. Linaclotide-induced intestinal pain reduction is thought to result from an increase in cyclic guanosine monophosphate (cGMP), which has been shown to decrease the activity of painsensing nerves.
In placebo-controlled phase III clinical trials of more than 2,800 adults, Linzess was shown to significantly reduce abdominal pain in IBS-C patients and significantly increase bowel movement frequency in both IBS-C patients and CIC patients. Improvements were reported in the first week of treatment and maintained throughout the treatment period. When a subset of Linzess-treated patients in the trials were switched to placebo, they reported their symptoms returned toward pretreatment levels within one week, while placebo-treated patients switched to Linzess reported symptom improvements.
Linzess has not been studied in paediatric patients. Linzess is contraindicated in paediatric patients up to 6 years of age. The use of Linzess in paediatric patients 6 through 17 years of age should be avoided. Ironwood and Forest expect Linzess to be available in the fourth quarter of 2012.
“The discovery of Linzess by Ironwood scientists, and the development work done together by Ironwood and our partner Forest, has resulted in a new medicine with the potential to improve the lives of millions of highly symptomatic IBS-C and CIC patients,” said Peter Hecht, chief executive officer of Ironwood. “As Ironwood’s first FDA-approved drug, Linzess represents significant progress towards achieving our goals of delivering medicines to patients and value to shareholders.”
Howard Solomon, chairman, CEO and president of Forest Laboratories, said: “The approval of Linzess validates Forest and Ironwood’s commitment to bringing forth an effective treatment in disease categories that previously had limited treatment options. We look forward to making this treatment available to the millions of adults with IBS-C and CIC in the United States. This achievement is the result of our close working relationship with Ironwood over the past five years in the development of this exciting product.”
LINZESS is the first and only guanylate cyclase-C (GC-C) agonist approved by the FDA for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. LINZESS is a once-daily capsule that helps relieve the chronic abdominal pain and constipation associated with IBS-C and constipation and hard stools associated with CIC. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients.
LINZESS binds to the GC-C receptor locally in the intestine, with no measurable blood plasma concentrations, resulting in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevations in intracellular cGMP are believed to stimulate secretion of intestinal fluid and accelerate gastrointestinal transit resulting in increased frequency of bowel movements. Elevations in extracellular cGMP are believed to decrease activity of pain-sensing nerves, which is thought to be responsible for a reduction in intestinal pain, according to nonclinical models. An issued composition of matter patent for linaclotide provides protection to 2025 in the United States. Ironwood and Forest will co-promote LINZESS in the United States. Ironwood has outlicensed linaclotide to Almirall, S.A. for European development and commercialization and to Astellas Pharma Inc. for development and commercialization in Japan, Indonesia, Korea, the Philippines, Taiwan, and Thailand.