– Data demonstrates that linaclotide reduces the need for rescue medications in this patient population –
– Additional presentations further characterize the efficacy and safety profiles of linaclotide as the only FDA-approved prescription therapy for this patient population –
– Functional constipation affects an estimated 6 million children and adolescents ages 6-17 years-old in the U.S.1 –
BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (Nasdaq: IRWD), a leading global gastrointestinal healthcare company, will present findings during the 2023 North American Society for Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) Annual Meeting demonstrating that linaclotide decreased the use of rescue medications in children and adolescents ages 6-17 years-old with functional constipation. These findings build on previously announced data from the company’s pivotal Phase III trial, which formed the basis of a June 2023 Food and Drug Administration (FDA) approval of linaclotide for the treatment of functional constipation in this pediatric population.
Functional constipation in children is defined as a condition with hard, infrequent bowel movements that are often difficult or painful to pass2. The condition affects an estimated 6 million children and adolescents ages 6-17 years-old in the U.S.1
The data, which were part of a post-hoc analysis, will be featured in a poster titled Once-Daily Linaclotide 72 µg Reduces the Need for Rescue Medication Use in Children with Functional Constipation (presentation number 465) on Oct. 6 from 12:30 to 1:30 p.m. PDT in the Sapphire Ballroom presented by Tina Shakhnovich, M.D., pediatric gastroenterologist and Ironwood’s Medical Director of Clinical Development. The analysis found that approximately half of the children enrolled in the trial relied on rescue medications at least once per week for symptom relief. By the end of the 12-week treatment period, the use of rescue medications, which included senna (oral), bisacodyl (oral or rectal) or sodium picosulphate (oral), decreased to 8.7 percent of children receiving linaclotide versus 18.8 percent of children receiving placebo. Over the entire study period, more children treated with linaclotide (61.0 percent) experienced a decrease in rescue medication use compared to those treated with placebo (48.2 percent), and fewer children treated with linaclotide (15.2 percent) experienced an increase in rescue medication use compared to those treated with placebo (26.2 percent; p=0.0095).
“In this clinical trial, participants experiencing an inadequate therapeutic response or exacerbation of symptoms could use rescue medications to alleviate their symptoms,” said Jeffrey S. Hyams, M.D., Head, Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children’s Medical Center, Professor of Pediatrics, University of Connecticut School of Medicine. “The decrease we saw in use of rescue medications is additional important evidence supporting the efficacy of linaclotide in this patient population.”
Ironwood and its collaborators will present additional data describing the cumulative treatment effect of linaclotide in this patient population. Additionally, Ironwood and its partner AbbVie are sponsoring a medical symposium titled “Managing Pediatric Constipation” on Oct. 6, 2023 from 6:00 to 8:00 p.m. PDT (Room: Indigo AE). The symposium, which is not an official NASPGHAN event/function, will provide meeting attendees with an overview of pediatric functional constipation, presentation/diagnosis and management.
“Ironwood is committed to ongoing research and education around our products and the diseases they treat to ensure deeper understanding of their impact,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. “We’re honored to be at NASPGHAN, reviewing data and information on pediatric functional constipation with the pediatric GI community.”
Cumulative Effect of Linaclotide in Children and Adolescents Ages 6-17 Years-Old with Functional Constipation
A poster titled Cumulative Treatment Effect of Linaclotide for Pediatric Functional Constipation: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial (presentation number 729) will be presented on Oct. 7, 2023 from 12:30 to 1:30 p.m. PDT in the Sapphire Ballroom by Tina Shakhnovich, M.D. The analysis showed that a higher proportion of patients in the linaclotide treatment group versus the placebo consistently achieved improvement at every responder threshold for increase in spontaneous bowel movement frequency and achievement of softer post-baseline stool consistency.
A poster titled Cumulative Experience with Diarrhea as an Uncommon Treatment-Emergent Adverse Event in Pediatric Trials of Linaclotide for the Treatment of Functional Constipation (presentation number 727) will be presented on Oct. 7, 2023, from 12:30 to 1:30 p.m. PDT in the Sapphire Ballroom by Julie Khlevner, M.D., Columbia University Vagelos College of Physicians and Surgeons and New York Presbyterian Morgan Stanley Children’s Hospital, New York, NY. The post-hoc analysis demonstrated that in pediatric patients with functional constipation, diarrhea occurred in 7.4 percent of the linaclotide-treated population and 1.5 percent of those receiving placebo.
About Linaclotide
LINZESS® is the #1 prescribed brand in the U.S. for the treatment of adult patients with irritable bowel syndrome with constipation (“IBS-C”) or chronic idiopathic constipation (“CIC”), based on IQVIA data. LINZESS is a once-daily capsule that helps relieve the abdominal pain, constipation, and overall abdominal symptoms of bloating, discomfort and pain associated with IBS-C, as well as the constipation, infrequent stools, hard stools, straining, and incomplete evacuation associated with CIC. LINZESS relieves constipation in children and adolescents aged 6 to 17 years with functional constipation. 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. In children with functional constipation aged 6 to 17 years, the recommended dose is 72 mcg.
LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called GC-C agonists. LINZESS contains a peptide called linaclotide that activates the GC-C receptor in the intestine. Activation of GC-C is thought to result 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 CIC. Ironwood also has partnered with AstraZeneca for development and commercialization of LINZESS in China, and with AbbVie for development and commercialization of linaclotide in all other territories worldwide.
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) and functional constipation (FC) in children and adolescents 6 to 17 years of age. It is not known if LINZESS is safe and effective in children with FC less than 6 years of age or in children with IBS-C less than 18 years of age.
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
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 guanylate cyclase (GC-C) agonism, which was associated with increased 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.
Diarrhea
In adults, 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.
In children and adolescents 6 to 17 years of age, diarrhea was the most common adverse reaction in 72 mcg LINZESS-treated patients in the FC double-blind placebo-controlled trial. Severe diarrhea was reported in <1% of 72 mcg LINZESS treated 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 or CIC adult patients: diarrhea, abdominal pain, flatulence, and abdominal distension.
In FC pediatric patients: diarrhea.
Please see full Prescribing Information including Boxed Warning:
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 global 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). LINZESS is also approved for the treatment of functional constipation in pediatric patients ages 6-17 years-old. Ironwood is also advancing apraglutide, a next-generation, long-acting synthetic GLP-2 analog being developed for rare gastrointestinal diseases, including short bowel syndrome with intestinal failure (SBS-IF) as well as several earlier stage assets. Building upon our history of GI innovation, 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, and has additional operations in Basel, Switzerland.
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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 potential of linaclotide for children and adolescents ages 6-17 years-old with functional constipation; the efficacy and safety profiles of linaclotide in this pediatric patient population; 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; 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; 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 U.S. Census, 2017 National Population Projection Tables; Robin, Samantha G. et al, Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria, The Journal of Pediatrics, December 2017; Koppen, I. J. N. et al., Prevalence of Functional Defecation Disorders in Children: A Systemic Review and Meta-Analysis. J Pediatr. 2018.
2 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.
