Ironwood to Present New Data at Digestive Disease Week® 2023 Demonstrating Potential of Linaclotide for Functional Constipation in Children and Adolescents Ages 6-17 Years-Old

Rhea-AI Summary

Ironwood Pharmaceuticals (Nasdaq: IRWD) will present pivotal Phase III data on linaclotide for treating functional constipation in children aged 6-17 at the 2023 Digestive Disease Week® (DDW) from May 6-9 in Chicago, IL. This condition affects around 6 million children in the U.S. An oral presentation will detail a clinical trial assessing the efficacy and safety of linaclotide 72 mcg in this age group. Four poster sessions will present further efficacy and safety data. Notably, the FDA granted Priority Review for a supplemental New Drug Application (sNDA) for linaclotide in pediatric use, with a PDUFA date set for June 14, 2023. Currently, there are no FDA-approved therapies for pediatric functional constipation. Ironwood continues to expand its research in this area.

– Pivotal Phase III data will be spotlighted via an oral presentation –

– Additional efficacy and safety data will be featured across four posters –

BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a GI-focused healthcare company, announced today that the company will present findings during the 2023 Digestive Disease Week® (DDW) from studies on the potential of linaclotide for children and adolescents ages 6-17 years-old with functional constipation. DDW is being held from May 6 through May 9 in Chicago, IL.

Functional constipation in children is defined as a condition with hard, infrequent bowel movements that are often difficult or painful to pass¹. The condition affects an estimated 6 million children ages 6-17 years-old in the U.S.¹

An oral presentation will discuss data from a Phase III clinical trial that evaluated the efficacy and safety of linaclotide 72 mcg in treating functional constipation in pediatric patients ages 6-17 years old. Ironwood had previously announced topline data from this trial in September 2022. Poster presentations will highlight data on the efficacy of linaclotide in addressing bothersome functional constipation symptoms in pediatric patients ages 6-17 years old, as well as aggregate data on the safety of linaclotide in this patient population.

Linaclotide is marketed as LINZESS® by Ironwood and AbbVie in the United States and is indicated for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). It is not approved for use in patients less than 18 years of age. Ironwood announced earlier this year that the U.S. Food and Drug Administration (FDA) has granted Priority Review to the supplemental New Drug Application for LINZESS for the treatment of children and adolescents ages 6-17 years-old with functional constipation and assigned a Prescription Drug User Fee Act (PDUFA) date of June 14^th, 2023. Additional pediatric clinical trials in IBS-C and functional constipation are ongoing. There are currently no FDA -approved prescription therapies for functional constipation.

An overview of all five presentations is provided below.

Efficacy and Safety of Linaclotide in Pediatric Functional Constipation

• Efficacy and Safety of Linaclotide in Treating Functional Constipation in Pediatric Patients Aged 6-17 Years: A Phase III, Pivotal, Randomized, Placebo-Controlled Trial
  (oral presentation, presentation number 145), by Carlo Di Lorenzo, M.D., Nationwide Children’s Hospital, Columbus, OH, on Saturday, May 6, from 10:15 to 10:30 a.m. CST in room W195

Time to Response and Impact of Linaclotide on Bothersome Functional Constipation Symptoms in a Pediatric Population

• Efficacy of Linaclotide in Treating Symptoms of Incomplete Evacuation and Straining in Pediatric Patients with Functional Constipation
  (poster presentation number Mo2007), presented by Julie Khlevner, M.D., New York Presbyterian Morgan Stanley Children’s Hospital, New York, NY, on Monday, May 8, from 12:30 to 1:30pm CST
• Time to Response of Linaclotide in Treating Functional Constipation in Pediatric Patients Aged 6-17 Years: Data From a Phase 3, Randomized, Placebo-Controlled Trial
  (poster presentation number Mo2008), by Samuel Nurko, M.D., Boston Children’s Hospital, Boston, MA, on Monday, May 8, from 12:30 to 1:30 p.m. CST

Aggregate Safety Data in Patients with Functional Constipation Ages 6-17 Years-Old

• Long-Term Safety of Linaclotide in Treating Functional Constipation in Pediatric Patients Aged 6-17 Years: Interim Analysis of an Open-Label, Phase 3, Extension Trial
  (poster presentation number Mo2016), by Miguel Saps, M.D., University of Miami, Miami, FL, on Monday, May 8, from 12:30 to 1:30 p.m. CST
• Safety of Linaclotide in Pediatric Patients with Functional Constipation: A Pooled Analysis of Placebo-Controlled, Randomized-Controlled Trials (poster presentation number Mo2015), presented by Jeffrey Samuel Hyams, M.D., Connecticut Children’s Medical Center, Hartford, CT, on Monday, May 8, from 12:30 to 1:30 p.m. CST

About Linaclotide

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. In the United States, Ironwood and AbbVie co-develop and co-commercialize LINZESS® for the treatment of adults with IBS-C or CIC. In Europe, AbbVie markets linaclotide under the brand name CONSTELLA® for the treatment of adults with moderate to severe IBS-C. In Japan, Ironwood's partner Astellas markets linaclotide under the brand name LINZESS for the treatment of adults with IBS-C or chronic constipation. In China, (including Hong Kong and Macau) Ironwood’s partner Astra Zeneca markets linaclotide under the brand name LINZESS for the treatment of adults with IBS-C. Ironwood is also partnered with AbbVie for development and commercialization of linaclotide in all other territories worldwide. LINZESS® and CONSTELLA® are registered trademarks of Ironwood Pharmaceuticals, Inc. Any other trademarks referred to in this press release are the property of their respective owners. All rights reserved.

LINZESS Important Safety Information

INDICATIONS AND USAGE

LINZESS (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE   LINZESS is contraindicated in patients less than 2 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration.

Contraindications

• LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
• LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions

Pediatric Risk

• LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism resulting in mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established.

Diarrhea

• Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

• In IBS-C clinical trials: 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 trials of a 145 mcg dose: 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%). In a CIC trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).

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

LINZESS® and CONSTELLA® are registered trademarks of Ironwood Pharmaceuticals, Inc. Any other trademarks referred to in this press release are the property of their respective owners. All rights reserved.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (Nasdaq: IRWD), an S&P SmallCap 600® company, is a leading gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS® (linaclotide), the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Under the guidance of our seasoned industry leaders, we continue to build upon our history of GI innovation and challenge what has been done before to shape what the future holds. We keep patients at the heart of our R&D and commercialization efforts to reduce the burden of GI diseases and address significant unmet needs.

Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts.

We routinely post information that may be important to investors on our website at www.ironwoodpharma.com. In addition, follow us on Twitter and on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the advancement of our linaclotide pediatrics development program in pediatric patients with functional constipation; the potential of linaclotide for children and adolescents ages 6-17 years-old with functional constipation; the size of the pediatric population affected by functional constipation. These forward-looking statements speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements. 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 those related to the effectiveness of development and commercialization efforts by us and our partners; preclinical and clinical development, manufacturing and formulation development of linaclotide and our product candidates; the risk that clinical programs and studies may not progress or develop as anticipated, including that studies are delayed or discontinued for any reason, such as safety, tolerability, enrollment, manufacturing, economic or other reasons; the risk that findings from our completed nonclinical and clinical studies may not be replicated in later studies; the risk that we or our partners are unable to obtain, maintain or manufacture sufficient LINZESS or our product candidates, or otherwise experience difficulties with respect to supply or manufacturing; the efficacy, safety and tolerability of linaclotide and our product candidates; the risk that the therapeutic opportunities for LINZESS or our product candidates are not as we expect; decisions by regulatory and judicial authorities; the risk we may never get additional patent protection for linaclotide and other product candidates, that patents for linaclotide or other products may not provide adequate protection from competition, or that we are not able to successfully protect such patents; the risk that the development of any of our clinical pediatric programs in IBS-C and functional constipation in 6 to 17 year-olds are not successful or that any of our product candidates is not successfully commercialized; the risk that the FDA will not approve our sNDA submission for the potential indication in functional constipation in pediatric patients aged 6-17; outcomes in legal proceedings to protect or enforce the patents relating to our products and product candidates, including abbreviated new drug application litigation; the risk that financial and operating results may differ from our projections; developments in the intellectual property landscape; challenges from and rights of competitors or potential competitors; developments in accounting guidance or practice; Ironwood’s or AbbVie’s accounting practices, including reporting and settlement practices as between Ironwood and AbbVie; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; the impact of the COVID-19 pandemic; and the risks listed under the heading “Risk Factors” and elsewhere in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022, and in our subsequent SEC filings.

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1 Di Lorenzo C, Hyams JS, Saps M, et al. Chapter 16: Childhood Functional Gastrointestinal Disorders: Child/Adolescent. In: Drossman DA, Chang L, Chey WD, et al. Rome IV: Functional Gastrointestinal Disorders: Disorders of Gut-Brain Interaction. Raleigh, NC: Rome Foundation; 2016.

 

View source version on businesswire.com: https://www.businesswire.com/news/home/20230424005052/en/

Media:

Beth Calitri, 978-417-2031

bcalitri@ironwoodpharma.com

Investors:

Greg Martini, 617-374-5230

gmartini@ironwoodpharma.com

Matt Roache, 617-621-8395

mroache@ironwoodpharma.com

Source: Ironwood Pharmaceuticals, Inc.

FAQ

What are the key findings Ironwood Pharmaceuticals will present about linaclotide at DDW 2023?

Ironwood Pharmaceuticals plans to present pivotal Phase III data showing the efficacy and safety of linaclotide for treating functional constipation in children aged 6-17 at the 2023 Digestive Disease Week.

What is the significance of the FDA Priority Review for linaclotide?

The FDA granted Priority Review for the supplemental New Drug Application for linaclotide in pediatric patients, indicating the importance of its potential use in treating functional constipation in children and adolescents.

When is the PDUFA date for linaclotide's pediatric indication?

The Prescription Drug User Fee Act (PDUFA) date for the pediatric indication of linaclotide is set for June 14, 2023.

How many children in the US are affected by functional constipation?

Approximately 6 million children aged 6-17 in the United States are affected by functional constipation.

What is the current status of FDA-approved treatments for functional constipation in children?

Currently, there are no FDA-approved prescription therapies for functional constipation in pediatric patients.