Ironwood and Allergan Enter Agreement to Co-Promote VIBERZI for Irritable Bowel Syndrome with Diarrhea (IBS-D) in the U.S.

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Ironwood Pharmaceuticals, Inc. IRWD announced today an agreement with Allergan plc for the U.S. 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-commercialization 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 U.S. 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 commercialization of VIBERZI. The co-promotion will begin as soon as VIBERZI is commercially available.

About VIBERZI (eluxadoline)

VIBERZI (eluxadoline) is an orally active compound indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) 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% 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% and 8% for eluxadoline 75 mg and 100 mg; 2% for placebo) and nausea (8% and 7% for eluxadoline 75 mg and 100 mg; 5% for placebo). Rates of severe constipation were less than 1% in patients receiving 75 mg and 100 mg eluxadoline. Rates of discontinuation due to constipation were low for both eluxadoline and placebo (≤2%) 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 U.S. Drug Enforcement Administration. Once VIBERZI receives final scheduling designation, the updated label will be available.

For more information including full prescribing information about VIBERZI see www.actavis.com/Actavis.

About IBS-D

Irritable bowel syndrome with diarrhea (IBS-D) is a functional bowel disorder characterized by chronic abdominal pain and frequent diarrhea, which affects approximately 15 million patients in the U.S. 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.

About LINZESS (linaclotide)

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 pediatric 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 commercialization of linaclotide in Japan and with AstraZeneca AB for development and commercialization in China.

LINZESS Important Safety Information

WARNING: PEDIATRIC RISK 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 pediatric patients under 18 years of age.

Contraindications

• LINZESS is contraindicated in pediatric patients under 6 years of age.
• LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions

Pediatric Risk

• LINZESS is contraindicated in children under 6 years of age. The safety and effectiveness of LINZESS in pediatric patients under 18 years of age have not been established. In neonatal mice, increased fluid secretion as a consequence of GC-C agonism resulted in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, children under 6 years of age may be more likely than older children and adults to develop significant diarrhea and its potentially serious consequences.
• Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 through 17 years of age.

Diarrhea

• Diarrhea was the most common adverse reaction of LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. Severe diarrhea was reported in 2% of LINZESS-treated patients. The incidence of diarrhea was similar in the IBS-C and CIC populations.
• Patients should be instructed to stop LINZESS if severe diarrhea occurs and to contact their healthcare provider. The healthcare provider should consider dose suspension and rehydration.

Adverse Reactions

• In IBS-C clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
• In CIC clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%).

Please see full Prescribing Information including Boxed Warning: http://www.frx.com/pi/linzess_pi.pdf

About IBS-C and CIC

While estimates vary, as many as 13 million adults in the U.S. 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 percent 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.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals IRWD is focused on creating medicines that make a difference for patients, building value to earn the continued support of our fellow shareholders, and empowering our team to passionately pursue excellence. We discovered, developed and are commercializing linaclotide, which is approved in the United States and a number of other countries. Our pipeline priorities include exploring further opportunities for linaclotide, as well as leveraging our therapeutic expertise in gastrointestinal disorders and our pharmacologic expertise in guanylate cyclases to address patient needs across the upper and lower gastrointestinal tract. Ironwood was founded in 1998 and is headquartered in Cambridge, Mass. Connect with us at www.ironwoodpharma.com or on Twitter at www.twitter.com/ironwoodpharma; information that may be important to investors will be routinely posted in both these locations.

VIBERZI™ is a trademark of Furiex Pharmaceuticals, Inc., an Allergan affiliate. LINZESS® is a trademark owned by Ironwood Pharmaceuticals, Inc. Cologuard® is a trademark of Exact Sciences, Corp. Any other trademarks referred to in this press release are the property of their respective owners. All rights reserved.

This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements about the synergies anticipated from promoting VIBERZI along with LINZESS and the potential addition of other gastrointestinal and primary care products to Ironwood's portfolio. Each forward‐looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include, but are not limited to, the risk that we do not realize the benefits of promoting an additional gastrointestinal product in our position in this market as much as we anticipate or at all and the risk that we are unable to obtain rights to additional gastrointestinal products on favorable terms. Applicable risks also include those that are listed under the heading "Risk Factors" and elsewhere in Ironwood's Annual Report on Form 10-K for the year ended December 31, 2014, in addition to the risk factors that are listed from time to time in Ironwood's Annual Reports on Form 10‐K, Quarterly Reports on Form 10‐Q and any other subsequent SEC filings. We undertake no obligation to update these forward-looking statements to reflect events or circumstances occurring after this press release. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release. All forward‐looking statements are qualified in their entirety by this cautionary statement.

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