- 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 in
frequency of spontaneous bowel movements (SBM) and improved stool
consistency in children and adolescents 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) for linaclotide (LINZESS®) to the U.S. Food and Drug
Administration (FDA) for the treatment of children and adolescents
6 to 17 years of age with functional constipation (FC). The sNDA
submission is based on results from a Phase 3 clinical trial, which
met the primary and secondary endpoints, evaluating linaclotide (72
mcg) for increased frequency of spontaneous bowel movements (SBM)
and improvement in stool consistency in patients aged 6 to17 years.
LINZESS is developed and marketed by AbbVie and Ironwood
Pharmaceuticals in the United
States and is currently indicated for the treatment 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 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 advance the standards of care in order to make a
difference in patients' lives."
In the multicenter double-blind Phase 3 study evaluating LINZESS
in patients 6 to 17 years of age with functional constipation, a
total of 330 patients were randomized in a 1:1 ratio between
linaclotide or placebo. Linaclotide showed a statistically
significant and clinically meaningful improvement 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 from baseline in SBMs/week
(2.220) compared to placebo (1.050) (p<0.0001).
The Phase 3 study demonstrated acceptable safety in the
pediatric population. The most common adverse event in the
pediatric Phase 3 study was diarrhea which occurred in 4.3% of
linaclotide-treated patients versus 1.8% in the placebo group.
FC in children is defined as a condition with hard, infrequent
bowel movements that are often difficult or painful to
pass.2 FC is a common problem in children of all ages,
with a worldwide prevalence ranging between 0.7% and 29.6%.3
Core symptoms of FC include decreased stool frequency,
harder stool consistency, painful passage of stools, and fecal
incontinence.2
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. AbbVie is partnered with Ironwood for the development
and commercialization of linaclotide in all other territories
worldwide. LINZESS® and CONSTELLA® are registered trademarks of
AbbVie. 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%).
See full Prescribing Information including Boxed Warning:
http://www.allergan.com/assets/pdf/linzess_pi
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines
that solve serious health issues today and address the 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, in addition to products and services across its
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow @AbbVie on
Twitter, Facebook, Instagram, YouTube, and LinkedIn.
Forward-Looking Statements
Some statements in this
news release are, or may be considered, forward-looking statements
for purposes of the Private Securities Litigation Reform Act of
1995. The words "believe," "expect," "anticipate," "project" and
similar expressions, among others, generally identify
forward-looking statements. 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 statements. Such risks and
uncertainties include, but are not limited to, failure to realize
the expected benefits from AbbVie's acquisition of Allergan plc
("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from 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 to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. Additional information about the economic, competitive,
governmental, technological and other factors that may affect
AbbVie's operations is set forth in Item 1A, "Risk Factors," of
AbbVie's 2021 Annual Report on Form 10-K, which has been filed with
the Securities and 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
statements as a result of subsequent events or developments, except
as required by law.
References:
- Data on 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, et
al. Rome IV: Functional Gastrointestinal Disorders: Disorders of
Gut-Brain Interaction. Raleigh,
NC: Rome Foundation; 2016.
- Mugie SM, Benninga MA, Di Lorenzo
C. Epidemiology of constipation in children and adults: a
systematic review. Best Pract Res Clin Gastroenterol.
2011;25:3-18.
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SOURCE AbbVie