Ironwood Pharmaceuticals, Inc., a pharmaceutical company, engages in the research, development, and commercialisation of human therapeutic products, has entered into an agreement with Allergan plc for the US co-promotion of Viberzi (eluxadoline), Allergan’s new treatment for adults suffering from irritable bowel syndrome with diarrhea (IBS-D).
This arrangement is separate from and complementary to the companies’ ongoing co-development and co-commercialisation of Linzess (linaclotide) for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC).
“This collaboration enables Ironwood and Allergan to work together to bring forward two innovative medicines demonstrated to improve the abdominal pain and bowel dysfunction that define IBS-C and IBS-D, two types of IBS that impact nearly 30 million adult Americans,” said Bill Meury, executive vice president of commercial, North American brands for Allergan.
“Allergan and Ironwood have an established and successful partnership co-promoting Linzess in the US market, and we have demonstrated the strength of our combined commercial teams in accessing and educating both gastroenterologists and primary care physicians.”
“The Viberzi co-promotion agreement is a natural extension of Ironwood’s focus on bringing innovative solutions to patients suffering from functional gastrointestinal disorders, and particularly disorders characterized by abdominal pain,” said Tom McCourt, chief commercial officer of Ironwood.
“We believe our promotion of Viberzi will drive value for Ironwood and reinforce our market leadership position in this category. The co-promote requires no additional Ironwood investment and is synergistic with our existing commercial efforts for Linzess and Cologuard, further strengthening our commercial capabilities as we prepare to market additional gastrointestinal and primary care products.”
Under the terms of the agreement, Ironwood’s clinical sales specialists will detail Viberzi to the approximately 25,000 health care practitioners to whom they currently detail Linzess and Cologuard. Linzess will remain the first-position product for the Ironwood sales team. Ironwood’s promotional efforts will be compensated based on the volume of calls delivered by Ironwood’s sales force, as well as agreed upon performance metrics. Allergan will be responsible for all other costs relating to the commercialisation of Viberzi. The co-promotion will begin as soon as Viberzi is commercially available.
Viberzi (eluxadoline) is an orally active compound indicated for the treatment of irritable bowel syndrome with diarrhea in men and women. Viberzi has mixed opioid receptor activity, it is a mu receptor agonist, a delta receptor antagonist, and a kappa receptor agonist.
Efficacy was established in two phase III clinical studies, demonstrating significant superiority over placebo on the composite endpoint of simultaneous improvement in both abdominal pain and diarrhea at both 75 mg and 100 mg twice daily doses. The primary efficacy responder endpoint was evaluated over the duration of double-blind, placebo-controlled treatment. Response rates were compared based on patients who met the daily composite response criteria (improvement in both abdominal pain and stool consistency on the same day) for at least 50 per cent of the days from weeks 1 to 12 (FDA endpoint) and weeks 1 to 26 (European Medicines Agency endpoint).
The most common adverse events in the two phase III clinical trials were constipation (7 per cent and 8 per cent for eluxadoline 75 mg and 100 mg; 2 per cent for placebo) and nausea (8 per cent and 7 per cent for eluxadoline 75 mg and 100 mg; 5 per cent for placebo). Rates of severe constipation were less than 1 per cent in patients receiving 75 mg and 100 mg eluxadoline. Rates of discontinuation due to constipation were low for both eluxadoline and placebo (=2 per cent) and similar rates of constipation occurred between the active and placebo arms beyond 3 months of treatment. A total of 2,426 subjects were enrolled across the two studies.
The Food and Drug Administration (FDA) has recommended that Viberzi be classified as a controlled substance. This recommendation has been submitted to the US Drug Enforcement Administration. Once Viberzi receives final scheduling designation, the updated label will be available.
Irritable bowel syndrome with diarrhea is a functional bowel disorder characterized by chronic abdominal pain and frequent diarrhea, which affects approximately 15 million patients in the US. Although the exact cause of IBS-D is not known, symptoms are thought to result from a disturbance in the way the gastrointestinal tract and nervous system interact.
IBS-D can be debilitating and there are limited therapeutic options for managing the chronic symptoms. IBS-D is associated with economic burden in direct medical costs and indirect social costs such as absenteeism and lost productivity, along with decreased quality of life.
Linzess is the first and only guanylate cyclase-C (GC-C) agonist approved by the FDA and is indicated 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 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. Linzess should be taken at least 30 minutes before the first meal of the day.
Linzess is thought to work in two ways based on nonclinical studies. Linzess 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.
In placebo-controlled phase III clinical trials of more than 2,800 adults, Linzess was shown to reduce abdominal pain in IBS-C patients and increase bowel movement frequency in both IBS-C patients and CIC patients. Improvement in abdominal pain and constipation occurred in the first week of treatment and was maintained throughout the 12-week treatment period. Maximum effect on abdominal pain was seen at weeks 6-9 and maximum effect on constipation occurred during the first week. 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 is contraindicated in pediatric patients under 6 years of age. The use of Linzess in pediatric patients 6 through 17 years of age should be avoided. In nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration in young juvenile mice. The safety and efficacy of Linzess in paediatric patients under 18 years of age have not been established. In adults with IBS-C or CIC treated with Linzess, the most commonly reported adverse event was diarrhea.
Ironwood and Allergan are co-promoting Linzess in the United States. Linaclotide is marketed by Almirall, S.A. 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 commercialisation of linaclotide in Japan and with AstraZeneca AB for development and commercialisation in China.
While estimates vary, as many as 13 million adults in the US may suffer from IBS-C, and as many as 35 million may suffer from CIC. Results derived from responses to a web based survey commissioned by Forest Pharmaceuticals and Ironwood Pharmaceuticals suggest that only about half of adult IBS-C sufferers are medically diagnosed, and only about 12 per cent of adult CIC sufferers are medically diagnosed. Hallmark symptoms associated with IBS-C include abdominal pain and constipation. Symptoms associated with CIC may include constipation, hard or lumpy stools, infrequent stools, and incomplete evacuation (not completely emptying the bowels). There are few available prescription treatment options for these conditions.