– Phase IIIb study met all primary and
secondary endpoints with statistical significance and demonstrated
that linaclotide improved the overall abdominal symptoms of
bloating, pain and discomfort in adults with IBS-C –
– Results further support the efficacy and
safety of LINZESS for the millions of adults suffering from
multiple frequent and bothersome symptoms associated with IBS-C
–
Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) and Allergan
plc (NYSE:AGN) today announced positive topline data from a
Phase IIIb clinical trial evaluating LINZESS (linaclotide) 290 mcg
on multiple abdominal symptoms in adult patients with IBS-C. The
trial met its primary multi-component endpoint and demonstrated
that linaclotide improved the overall abdominal symptoms of
bloating, pain and discomfort in adult IBS-C patients compared to
placebo. The trial also met both secondary endpoints. This trial
was designed to highlight the impact of LINZESS on the overall
abdominal symptoms of bloating, pain and discomfort, which are part
of patients’ reported real-world experience, thereby enabling
better communication about these symptoms.
LINZESS is marketed by Ironwood and Allergan in the United
States and is indicated for the treatment of adults with IBS-C or
chronic idiopathic constipation (CIC). Research has shown that
approximately 95 percent of adults with IBS-C experience bothersome
abdominal bloating, pain, and/or discomfort, with the majority
experiencing these symptoms once a week or more. There are an
estimated 13 million adults in the U.S. with IBS-C.1,2
“While research clearly suggests that the symptoms of abdominal
bloating, pain, and discomfort have a considerable impact on adults
suffering from IBS-C, in the clinical setting patients often use
the word ‘constipation’ as a general term to represent their
abdominal and bowel symptoms. This can lead to a less precise
communication regarding their symptoms between patient and
physician and can impact management,” said Lin Chang, M.D.,
Professor of Medicine at the Vatche and Tamar Manoukian Division of
Digestive Diseases at the University of California, Los Angeles
(UCLA). “I believe the data from this LINZESS Phase IIIb trial will
be very important in helping patients and physicians have a more
comprehensive dialogue about the multiple symptoms associated with
IBS-C.”
Topline data from a randomized, double-blind, placebo-controlled
Phase IIIb trial showed that linaclotide 290 mcg administered
orally once daily demonstrated a statistically significant and
clinically meaningful improvement in overall abdominal symptoms
compared to placebo across the primary and both secondary
endpoints. In the multi-component primary endpoint,
linaclotide-treated patients showed a 29.7% mean decrease from
baseline in their weekly abdominal score (bloating, pain and
discomfort) through the 12-week treatment period, compared to 18.3%
for the placebo-treated patients (p<0.0001). In the secondary
endpoints, 40.5% of patients treated with linaclotide 290 mcg
demonstrated a clinically meaningful response, as defined by the
abdominal symptom score responder, compared to 23.4% of
placebo-treated patients (p<0.0001). An abdominal symptom score
responder was defined as a patient who experienced an improvement
of at least two-points from baseline in their weekly abdominal
score for at least six of 12 weeks of treatment period. These
findings add to the significant body of data supporting the impact
of linaclotide on the overall abdominal symptoms of bloating, pain
and discomfort in adult IBS-C patients.
Linaclotide was well-tolerated in this Phase IIIb study, with
the most commonly reported adverse event being diarrhea. During the
treatment period, diarrhea was reported in 4.6% of patients on
linaclotide 290 mcg as compared to 1.6% of patients on placebo.
Study discontinuation resulting from diarrhea occurred in 1.6% of
linaclotide 290 mcg patients compared to none of the
placebo-treated patients.
“These topline results demonstrated that LINZESS can help
provide overall relief of some of the multiple abdominal symptoms
that IBS-C patients identify as among the most bothersome,” said
Mike Shetzline, M.D., Ph.D., chief medical officer, senior vice
president and head of drug development at Ironwood. “As the 10th
Phase III trial of linaclotide to meet its primary endpoint, this
study further contributes to the robust body of evidence supporting
the use of LINZESS in adults with IBS-C and further strengthens its
clinical profile.”
“IBS-C is a frustrating and uncomfortable condition, but it can
be treated. We expect that communicating the full clinical profile
of LINZESS on the overall abdominal symptoms of bloating, pain, and
discomfort will broaden physicians’ understanding of the
appropriate patient and may help those who need to find relief,”
said David Nicholson, chief research & development officer at
Allergan.
The randomized, double-blind, placebo-controlled, parallel-group
study was designed to evaluate the efficacy and safety of LINZESS
290 mcg on multiple abdominal symptoms in adult patients with
IBS-C. 614 patients were randomized to placebo or LINZESS 290 mcg
once daily for 12 weeks, followed by a four-week randomized
withdrawal period. The primary efficacy endpoint was change from
baseline in abdominal score based on daily patient assessments of
abdominal bloating, pain and discomfort at their worst, as reported
on an 11-point numerical rating scale. Additional endpoints
included change from baseline in spontaneous bowel movement
frequency, complete spontaneous bowel movement frequency, stool
consistency, and straining.
Additional data from this Phase IIIb trial are expected to be
shared at upcoming scientific meetings and via peer-reviewed
publications.
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. Linaclotide is
marketed by Ironwood and Allergan plc in the United States as
LINZESS® and is indicated for the treatment of adults with
irritable bowel syndrome with constipation (IBS-C) or chronic
idiopathic constipation (CIC). Linaclotide is marketed by Allergan
for the treatment of adults with moderate to severe IBS-C in Europe
under the brand name CONSTELLA®. Ironwood is partnered with
AstraZeneca for development and commercialization of linaclotide in
China, Hong Kong and Macau. Astellas has the exclusive rights to
develop and commercialize linaclotide in Japan. Allergan has rights
to develop and market in the remaining rest of world countries.
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
LINZESS is contraindicated in patients
less than 6 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. Use of LINZESS should
be avoided in patients 6 years to less than 18 years of age. The
safety and effectiveness of LINZESS have not been established in
patients less than 18 years of age.
Contraindications
- LINZESS is contraindicated in patients
less than 6 years of age due to the risk of serious
dehydration.
- LINZESS is contraindicated in patients
with known or suspected mechanical gastrointestinal
obstruction.
Warnings and PrecautionsPediatric Risk
- LINZESS is contraindicated in patients
less than 6 years of age. The safety and effectiveness of LINZESS
in patients less than 18 years of age have not been established. In
neonatal mice, linaclotide increased fluid secretion as a
consequence of GC-C agonism resulting in mortality within the first
24 hours due to dehydration. Due to increased intestinal expression
of GC-C, patients less than 6 years of age may be more likely than
patients 6 years of age and older to develop severe diarrhea and
its potentially serious consequences.
- Use of LINZESS should be avoided in
pediatric patients 6 years to less than 18 years of age. Although
there were no deaths in older juvenile mice, given the deaths in
young juvenile mice and the lack of clinical safety and efficacy
data in pediatric patients, use of LINZESS should be avoided in
pediatric patients 6 years to less than 18 years of age.
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
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a
global pharmaceutical leader focused on developing, manufacturing
and commercializing branded pharmaceutical, device, biologic,
surgical and regenerative medicine products for patients around the
world. Allergan markets a portfolio of leading brands and
best-in-class products primarily focused on four key therapeutic
areas including medical aesthetics, eye care, central nervous
system and gastroenterology. As part of its approach to delivering
innovation for better patient care, Allergan has built one of the
broadest pharmaceutical and device research and development
pipelines in the industry.
With colleagues and commercial operations in approximately 100
countries, Allergan is committed to working with physicians,
healthcare providers and patients to deliver innovative and
meaningful treatments that help people around the world live
longer, healthier lives every day.
For more information, visit Allergan's website at
www.Allergan.com.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (Nasdaq: IRWD) is a GI-focused
healthcare company dedicated to creating medicines that make a
difference for patients living with GI diseases. We discovered,
developed and are commercializing linaclotide, the U.S. branded
prescription market leader for adults with irritable bowel syndrome
with constipation (IBS-C) or chronic idiopathic constipation (CIC).
We are currently advancing a Phase IIIb trial evaluating the
efficacy and safety of linaclotide on multiple abdominal symptoms,
including bloating, pain, and discomfort, in adult patients with
IBS-C.
We are also advancing two late-stage, first-in-category GI
product candidates: IW-3718 is a gastric retentive formulation of a
bile acid sequestrant being developed for the potential treatment
of persistent gastroesophageal reflux disease, and MD-7246 is a
delayed-release formulation of linaclotide that is being evaluated
as an oral, intestinal, non-opioid, pain-relieving agent for
patients suffering from abdominal pain associated with IBS with
diarrhea.
Ironwood was founded in 1998 and is headquartered in Cambridge,
Mass. For more information, please visit our website at
www.ironwoodpharma.com or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely
posted in both these locations.
IRONWOOD®, the three-leaf logo, 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.
Forward-Looking Statements
This press release contains forward-looking statements.
Investors are cautioned not to place undue reliance on these
forward-looking statements, including, but not limited to,
statements about the potential for linaclotide to offer IBS-C
patients relief from bothersome symptoms including abdominal
bloating, pain and discomfort; the efficacy and safety of
linaclotide; IBS-C symptoms and the size of the potential patient
population; the size, scope and design of the Phase IIIb study of
linaclotide in adults with IBS-C; the potential of the Phase IIIb
data to improve physician-patient dialogue; the strength of
linaclotide’s clinical profile; the potential of the Phase IIIb
data to increase requests for linaclotide; and the development and
regulatory plans for linaclotide. 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 preclinical and clinical development, manufacturing and
formulation development; the risk that future clinical studies need
to be discontinued for any reason, including safety, tolerability,
enrollment, manufacturing or economic reasons; the risk that
findings from our completed nonclinical and clinical studies may
not be replicated in later studies; efficacy, safety and
tolerability of our products and product candidates; the risk that
the therapeutic opportunities for linaclotide are not as we expect;
decisions by regulatory and judicial authorities; the risk that we
are unable to successfully commercialize linaclotide; the risk that
we may never get sufficient patent protection for our products and
our product candidates or that we are not able to successfully
protect such patents; the outcomes in legal proceedings to protect
or enforce the patents relating to our products and product
candidates, including ANDA litigation; developments in the
intellectual property landscape; challenges from and rights of
competitors or potential competitors; the risk that our planned
investments do not have the anticipated effect on our company
revenues, products or product candidates; the risk that we are
unable to manage our operating expenses or cash use for operations,
or are unable to commercialize our products, within the guided
ranges or otherwise as expected; and the risks listed under the
heading "Risk Factors" and elsewhere in Ironwood's Quarterly Report
on Form 10-Q for the quarter ended March 31, 2019, Allergan’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2019
and in the subsequent SEC filings of each company. These
forward-looking statements (except as otherwise noted) speak only
as of the date of this press release, and Ironwood and Allergan
undertake no obligation to update these forward-looking
statements.
1 GfK “IBS in America”, 2016.2 Lieberman GI Patient Landscape
Survey, 2010
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version on businesswire.com: https://www.businesswire.com/news/home/20190618005929/en/
AllerganManisha Narasimhan, PhDInvestor Relations(862)
261-7162Amy RoseGlobal Corporate Media Relations(862)
289-3072FleishmanHillardAdam SilversteinMedia
Relations917-697-9313Adam.Silverstein@fleishman.comIronwoodMeredith
KayaInvestor and Media Relationsmkaya@ironwoodpharma.com
Garret BonneyInvestor
Relations617-374-4818gbonney@ironwoodpharma.com
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