- 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 within frequency of spontaneous bowel movements (SBM) and improved stool consistency in kids and children aged 6 to 17 years
NORTH CHICAGO, Ill. , Dec. 16, 2022 /PRNewswire/ — AbbVie (NYSE: ABBV ) today announced that it has submitted a supplemental New Drug Application (sNDA) with regard to linaclotide (LINZESS®) to the U. H. Food and Medication Administration (FDA) for the treatment of children and adolescents 6 in order to 17 years old with functional constipation (FC). The sNDA submission is founded on results from a Phase 3 clinical trial, which met the particular primary and secondary endpoints, evaluating linaclotide (72 mcg) for increased frequency associated with spontaneous intestinal movements (SBM) and improvement in stool consistency in patients aged 6 to17 years. LINZESS is developed plus marketed by AbbVie and Ironwood Pharmaceuticals in the United States and will be currently indicated for that therapy of adults with chronic idiopathic obstipation (CIC) or irritable bowel syndrome with constipation (IBS-C).
“Although practical constipation is common among pediatric patients, they have long been difficult to manage due to a lack of authorized prescription treatment options, ” said Celine Goldberger , MD, PhD, vice president, head of US medical affairs, AbbVie. “This milestone demonstrates our tireless work to advance the standards of care in order to make a difference in patients’ lives. ”
In the multicenter double-blind Stage 3 research evaluating LINZESS in patients 6 in order to 17 many years of age with useful constipation, the total associated with 330 patients were randomized in a 1: 1 ratio between linaclotide or even placebo. Linaclotide showed the statistically significant and clinically meaningful enhancement compared to placebo in 12-week SBM frequency rate (SBMs/week), the primary endpoint. Linaclotide-treated patients demonstrated a greater than two-fold least squares mean change through baseline within SBMs/week (2. 220) compared to placebo (1. 050) (p< 0. 0001).
The Phase 3 study demonstrated acceptable safety in the particular pediatric population. The most common adverse event in the pediatric Phase a few study was diarrhea which usually occurred in 4. 3% of linaclotide-treated patients versus 1. 8% in the placebo group.
FC inside children is defined as a condition along with hard, infrequent bowel movements that are often difficult or painful to pass. 2 FC is the common problem in kids of all ages, with a worldwide prevalence ranging between 0. 7% plus 29. 6%. three or more Core symptoms of FC include decreased feces frequency, harder stool regularity, painful passage of stools, and fecal incontinence. 2
Linaclotide is a guanylate cyclase-C (GC-C) agonist that is thought to work in two ways based on nonclinical studies. Linaclotide binds in order to the GC-C receptor locally within the particular intestinal epithelium. Activation of GC-C results in improved intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves within the intestine. The medical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established. In the United States , Ironwood plus AbbVie co-develop and co-commercialize LINZESS® for your treatment associated with adults along with IBS-C or even CIC. Inside Europe , AbbVie markets linaclotide under the brand name CONSTELLA® for the treatment of adults with moderate to severe IBS-C. AbbVie is usually partnered along with Ironwood regarding the development and commercialization of linaclotide in all other territories worldwide. LINZESS® and CONSTELLA® are registered trademarks associated with AbbVie. Any other trademarks referred in order 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 pointed out in grownups for that treatment of both irritable intestinal syndrome with constipation (IBS-C) and persistent idiopathic constipation (CIC).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE
LINZESS is contraindicated in individuals less than 2 years of age. In nonclinical studies in neonatal mice, administration of a single, medically relevant, adult oral dose of linaclotide caused deaths due to dehydration.
- LINZESS is contraindicated in patients less than 2 years of age group due to the risk of serious dehydration.
- LINZESS is contraindicated in sufferers with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in patients lower than two years old. In neonatal mice, linaclotide increased liquid secretion as a consequence of age-dependent elevated GC-C agonism resulting inside 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 yrs of age in order to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The particular safety plus effectiveness associated with LINZESS inside patients much less than 18 years old have not been established.
- 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 has been similar within the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg plus 290 mcg LINZESS-treated individuals, and in < 1% of 72 mcg LINZESS-treated CIC sufferers. 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% versus 1%).
- In CIC tests of the 145 mcg dose: diarrhea (16% compared to 5% placebo), abdominal pain (7% vs 6%), flatulence (6% versus 5%), upper respiratory tract infection (5% compared to 4%), sinusitis (3% vs 2%) plus abdominal distension (3% versus 2%). Within a CIC trial of the 72 mcg dose: diarrhea (19% compared to 7% placebo) and stomach distension (2% vs < 1%).
See full Prescribing Info including Boxed Warning:
AbbVie’s mission is to discover and deliver innovative medicines that solve severe health issues today plus address the particular 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 and gastroenterology, within addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @AbbVie upon Twitter , Facebook , Instagram , YouTube , and LinkedIn .
Some statements with this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act associated with 1995. The words “believe, inch “expect, inches “anticipate, ” “project” plus 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 outcomes to differ materially from those indicated in the particular forward-looking statements. Such dangers and questions include, but are not limited to, failure to realize the expected benefits from AbbVie’s acquisition of Allergan plc (“Allergan”), failure in order to promptly and effectively integrate Allergan’s businesses, competition through other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable in order to our industry and the particular impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that could affect AbbVie’s operations is set forth in Item 1A, “Risk Factors, ” associated with AbbVie’s 2021 Annual Report on Form 10-K, which has been filed with the Securities plus Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking claims as a result of subsequent events or even developments, except as required by law.
- Data upon file. AbbVie, Inc. 104746
- Di Lorenzo C, Hyams JS, Saps M, et al. Chapter 16: Childhood Functional Gastrointestinal Disorders: Child/Adolescent. In: Drossman DA, Chang L, Chey WD, ainsi que al. Rome IV: Functional Gastrointestinal Disorders: Disorders of Gut-Brain Interaction. Raleigh, NC : Ancient rome Foundation; 2016.
- Mugie SM, Benninga MA, Di Lorenzo C . Epidemiology associated with constipation within children and adults: a systematic review. Best Pract Res Clin Gastroenterol. 2011; 25: 3-18.