Ironwood Pharmaceuticals, Inc. and Allergan plc have announced that the U.S. Food and Drug Administration (FDA) has approved a 72 mcg dose of LINZESS® (linaclotide) for the treatment of chronic idiopathic constipation (CIC) in adult patients. The newly approved dose will provide physicians with dosing flexibility based on individual presentation or tolerability, in treating the large and heterogenous population of adult CIC patients. The new dose is expected to be available in the first quarter of 2017.

LINZESS is now FDA-approved in three dosage strengths: 290 mcg for adult patients with irritable bowel syndrome with constipation (IBS-C), and 145 mcg and a new 72 mcg for the treatment of adults with CIC. Since the launch of LINZESS in December of 2012, nearly 1.5 million unique patients have filled nearly 7 million prescriptions, according to IMS Health data.1 The approval of LINZESS 72 mcg is based on results from a Phase III clinical trial of 1,223 adults with CIC. This trial met its primary endpoint; the 72mcg dose demonstrated statistically significant improvement in Complete Spontaneous Bowel Movements compared to placebo over 12 weeks.

The most common adverse event was diarrhea; the rates of diarrhea and of discontinuations due to diarrhea were numerically lower for the 72 mcg dose than the 145 mcg dose in this trial. LINZESS has met all primary endpoints in each of its five pivotal U.S. Phase III trials, spanning three doses and two indications. 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. There are few available prescription treatment options for this condition. LINZESS® is the #1 prescribed brand for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC), based on IMS Health data.

Since its FDA approval in August of 2012 and subsequent launch in December 2012, nearly 1.5 million unique patients have filled nearly 7 million prescriptions for LINZESS, according to IMS Health. LINZESS is a once-daily capsule that helps relieve the abdominal pain and constipation associated with IBS-C, as well as the constipation, infrequent stools, hard stools and incomplete evacuation associated with CIC. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients, with a 72 mcg dose approved for use in CIC depending on individual patient presentation or tolerability.

LINZESS should be taken at least 30 minutes before the first meal of the day. LINZESS is contraindicated in pediatric patients less than 6 years of age.  The safety and effectiveness of LINZESS in pediatric patients less than 18 years of age have not been established. In neonatal mice, linaclotide increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration.

Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years if age and older to develop severe diarrhea and its potentially serious consequences. In adults with IBS-C or CIC treated with LINZESS, the most commonly reported adverse event was diarrhea. LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called guanylate cyclase-C (GC-C) agonists.

LINZESS contains a peptide called linaclotide that is structurally related to the naturally occurring peptides guanylin and uroguanylin, which activate the GC-C receptor in the intestine. Activation of GC-C is thought to result in two important outcomes, based on nonclinical studies. Linaclotide's activation of GC-C is thought to result in increased intestinal fluid secretion and accelerated transit and also to result in a decrease in the activity of pain-sensing nerves in the intestine.

Ironwood and Allergan plc are co-promoting LINZESS in the United States and Mexico. Linaclotide is marketed by Allergan for the treatment of adults with moderate to severe IBS-C in Europe and Canada under the brand name CONSTELLA®. Ironwood's partner Astellas received approval of linaclotide in Japan under the brand name LINZESS® for the treatment of adults with IBS-C. Ironwood also has partnered with AstraZeneca for development and commercialization of linaclotide in China.