Ironwood Pharmaceuticals, Inc. and Allergan plc announced that the US Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) for the 72 mcg dose of linaclotide for use in the treatment of adults with chronic idiopathic constipation (CIC). The sNDA for the 72 mcg dose of linaclotide is based on efficacy and safety data from a double-blind, placebo-controlled phase III clinical trial of 1,223 adult patients with CIC. The FDA Prescription Drug User Fee Act (PDUFA) target action date is expected to occur in early 2017.

If approved by the FDA, the 72 mcg dose of linaclotide would provide an additional treatment option for adult patients with CIC. Linaclotide is currently approved by the FDA for the treatment of adults with CIC as a 145 mcg capsule to be taken once per day. In addition, it is approved for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) as a 290 mcg capsule to be taken once per day. Since FDA approval in December of 2012, more than 1 million unique patients have filled a prescription for linaclotide, according to IMS Health.

Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder estimated to impact as many as 35 million adult Americans. CIC is generally characterized by infrequent bowel movements (less than three times per week), but symptoms vary across this broad and heterogeneous patient population and may also include recurrent straining, lumpy or hard stools, and/or a sensation that the bowels are not fully empty. Results derived from responses to a web-based survey commissioned by Allergan and Ironwood suggest that only 12 percent of adult CIC sufferers are medically diagnosed. There are few available prescription treatment options for this condition.

Linaclotide is a guanylate cyclase-C (GC-C) agonist that is thought to work in two ways based on nonclinical studies. Linaclotide binds to the GC-C receptor locally, within the intestinal epithelium. Activation of GC-C results in increased intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves in the intestine. The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established. Linaclotide is marketed by Ironwood and Allergan in the United States as Linzess and is indicated for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Linaclotide is marketed by Allergan for the treatment of adults with moderate to severe IBS-C in Europe under the brand name Constella. Ironwood also has partnered with Astellas Pharma Inc. for development and commercialization of linaclotide in Japan and with AstraZeneca for development and commercialization in China.

Linzess is contraindicated in pediatric patients under 6 years of age. In nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration in young juvenile mice. Use of Linzess should be avoided in pediatric patients 6 through 17 years of age. The safety and efficacy of Linzess has not been established in paediatric patients under 18 years of age.