- If approved, linaclotide would be the first prescription therapy for functional constipation in children and adolescents 6 to 17 years of age 1
- Submission is based on positive Phase 3 study data demonstrating linaclotide (72mcg) resulted in increases inside frequency associated with spontaneous bowel movements (SBM) and improved stool consistency in children and adolescents aged 6 to seventeen years
NORTH CHICAGO, Ill. , Dec. 16, 2022 /PRNewswire/ — AbbVie (NYSE: ABBV) today announced that it has submitted a supplemental New Drug Application (sNDA) for linaclotide (LINZESS®) to the U. S. Food and Drug Administration (FDA) for the treatment of kids and children 6 to be able to 17 years of age with practical constipation (FC). The sNDA submission is based on results from the Phase 3 clinical trial, which met the primary plus secondary endpoints, evaluating linaclotide (72 mcg) for increased frequency regarding spontaneous intestinal movements (SBM) and improvement in stool consistency in patients aged 6 to17 years. LINZESS will be developed in addition to marketed by AbbVie and even Ironwood Pharmaceuticals in the particular United States and is currently indicated with regard to the remedying of adults with chronic idiopathic constipation (CIC) or irritable bowel syndrome with constipation (IBS-C).
“Although functional constipation is common among pediatric patients, it has long been difficult for you to manage due to a lack of approved prescription treatment options, ” said Celine Goldberger , MD, PhD, vice president, head of US medical affairs, AbbVie. “This milestone demonstrates our tireless work to help advance the standards of care in order to make a difference found in patients’ lives. ”
In the multicenter double-blind Phase 3 study evaluating LINZESS in patients 6 to 17 years of age with useful constipation, a total of 330 patients were randomized in a 1: one ratio between linaclotide or placebo. Linaclotide showed a new statistically significant and clinically meaningful enhancement compared in order to placebo within 12-week SBM frequency rate (SBMs/week), typically the primary endpoint. Linaclotide-treated patients demonstrated a greater than two-fold least squares mean change from baseline inside of SBMs/week (2. 220) compared to placebo (1. 050) (p< 0. 0001).
The Stage 3 study demonstrated acceptable safety in the pediatric population. The most common adverse event within the pediatric Period 3 study was diarrhea which occurred in 4. 3% of linaclotide-treated patients versus 1. 8% in this placebo group.
FC inside children is usually defined as a condition along with hard, infrequent bowel movements that are often difficult or even painful to be able to pass. 2 FC is some sort of common problem in children of all ages, with a good worldwide prevalence ranging among 0. 7% and 29. 6%. 3 Core symptoms of FC include decreased stool frequency, harder stool consistency, painful passage involving stools, together with fecal incontinence. 2
Linaclotide is definitely a guanylate cyclase-C (GC-C) agonist that is thought for you to work in two ways based on nonclinical studies. Linaclotide binds to often the GC-C receptor locally within the intestinal epithelium. Activation of GC-C results throughout increased digestive tract fluid secretion and accelerated transit and additionally a decrease in your activity connected with pain-sensing nerves in the exact intestine. The clinical relevance of the effect on pain fibers, which is based upon nonclinical studies, has not been established. In the United Says , Ironwood and AbbVie co-develop not to mention co-commercialize LINZESS® for the treatment of adults with IBS-C or CIC. In Europe , AbbVie markets linaclotide under the particular brand name CONSTELLA® for that therapy of adults with moderate to severe IBS-C. AbbVie is partnered with Ironwood for typically the development and also commercialization with linaclotide around all other territories worldwide. LINZESS® as well as CONSTELLA® are registered trademarks of AbbVie. Any some 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) can be indicated at adults for your treatment for both irritable bowel syndrome with obstipation (IBS-C) and chronic idiopathic constipation (CIC).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN two YEARS OF AGE
LINZESS is contraindicated present in patients less than 2 many years of age. Inside nonclinical research in neonatal mice, administration of a single, clinically relevant, adult oral dose about linaclotide caused deaths because of to dehydration.
- LINZESS is certainly contraindicated here in patients lower than 2 yrs old due to this risk of serious dehydration.
- LINZESS is contraindicated in individuals with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in individuals below 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism resulting using mortality inside the 1st 24 hours due to lacks. There was no age-dependent trend in GC-C intestinal expression in a clinical study in children two to less than 18 years of age; however , there are insufficient data available on GC-C intestinal tract expression on children a lot less than 2 decades old to help assess the risk of developing diarrheand its potentially severe consequences during these patients. The safety and effectiveness of LINZESS in sufferers a minor from age have not been founded.
- Diarrhea was the most typical adverse reaction in LINZESS-treated patients appearing in the pooled IBS-C plus CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in often the IBS-C in addition to CIC populations. Severe diarrhea was reported in 2% of 145 mcg and even 290 mcg LINZESS-treated sufferers, and in < 1% of 72 mcg LINZESS-treated CIC patients. In case severe diarrhea occurs, dosing should be suspended, and the patient rehydrated.
Common Adverse Reactions (incidence ≥2% and greater than placebo)
- Found 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%) together with abdominal distension (2% versus 1%).
- In CIC tests of your 145 mcg dose: diarrhea (16% compared to 5% placebo), abdominal pain (7% as opposed to 6%), flatulence (6% against 5%), upper respiratory tract infection (5% or 4%), sinusitis (3% vs . 2%) and additionally abdominal entorse (3% as contrasted with 2%). In a CIC trial of a 72 mcg dose: diarrhea (19% v . 7% placebo) and stomach distension (2% vs < 1%).
See full Prescribing Information including Boxed Warning:
AbbVie’s mission is to discover not to mention deliver innovative medicines that solve significant health issues today and also address your medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women’s health as well as gastroenterology, for addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @AbbVie about Twitter , Facebook , Instagram , YouTube , and LinkedIn .
Some statements with this news release are, or perhaps may be considered, forward-looking statements for purposes of the exact Private Securities Litigation Reform Act associated with 1995. The words “believe, inch “expect, inches “anticipate, very well “project” and similar expressions, among others, generally identify forward-looking claims. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking assertions. Such dangers and questions include, but are not limited in order to, failure to be able to realize the particular expected benefits from AbbVie’s acquisition of Allergan plc (“Allergan”), failure to promptly and effectively integrate Allergan’s businesses, competition from additional products, challenges to intellectual property, difficulties inherent in the research and development process, undesirable litigation or maybe government action, changes for you to laws and regulations applicable to our industry as well as the impact of public health outbreaks, epidemics as well as pandemics, such as COVID-19. Additional information about typically the economic, competitive, governmental, technological and other factors that could affect AbbVie’s operations is set forth in Item 1A, “Risk Factors, micron of AbbVie’s 2021 Annual Report in Form 10-K, which has been filed with the Investments and Exchange Commission, because updated simply by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to help release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except since required by law.
- Data on file. AbbVie, Inc. 104746
- Di Lorenzo C, Hyams JS, Saps M, et al. Chapter 16: Childhood Functional Gastrointestinal Disorders: Child/Adolescent. Inside of: Drossman DA, Chang L, Chey WD, et ing. Rome IV: Functional Gastrointestinal Disorders: Problems of Gut-Brain Interaction. Raleigh, NC : Rome Foundation; 2016.
- Mugie SM, Benninga MA, Di Lorenzo C . Epidemiology of congestion in children and adults: a systematic review. Best Pract Res Clin Gastroenterol. 2011; 25: 3-18.