CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) announced today that the Phase
III clinical trial of its 72 mcg dose of linaclotide in adults with
chronic idiopathic constipation (CIC) met the primary endpoint. Ironwood
and partner Allergan plc intend to submit a supplemental new drug
application to the U.S. Food and Drug Administration (FDA) in the first
half of 2016.
Linaclotide is currently approved by the FDA as a 145 mcg capsule to be
taken once per day for the treatment of adults with CIC and as a 290 mcg
capsule to be taken once per day for the treatment of adults with
irritable bowel syndrome with constipation (IBS-C).
Top-line data from the Phase III trial indicate that the 72 mcg dose of
linaclotide demonstrated statistically significant improvement compared
to placebo on the 12-week Complete Spontaneous Bowel Movements (CSBM)
Overall Responder endpoint, the primary endpoint for the trial.
Additionally, in a pre-specified sensitivity analysis, the 72 mcg dose
of linaclotide demonstrated statistically significant improvement
compared to placebo on the Durable CSBM Overall Responder endpoint,
which is currently being requested by the FDA for Phase III CIC trials.
Both the 72 mcg and 145 mcg linaclotide doses were generally
well-tolerated in this trial. Consistent with previous Phase III trials
of linaclotide, the most common adverse event reported in
linaclotide-treated patients was diarrhea. The majority of diarrhea
cases reported were characterized as mild in severity. The rates of
diarrhea and of discontinuations due to diarrhea were lower for the 72
mcg dose than the 145 mcg dose in this trial.
"Linaclotide is the branded prescription market leader in the treatment
of IBS-C and CIC, and we believe the availability of a 72 mcg dose could
enhance its utility to physicians for use across the broad,
heterogeneous CIC patient population, which encompasses some 35 million
adult Americans," said Tom McCourt, chief commercial officer at
Ironwood. "With the successful completion of this trial, linaclotide has
met all primary endpoints in all seven of its Phase III trials -
spanning three doses and two indications. We are committed to continuing
to innovate with this molecule, and we are developing multiple
additional indications and formulations that, if approved, can address a
broad spectrum of patient needs."
The randomized, double-blind, placebo-controlled, multi-site Phase III
clinical trial enrolled 1,223 adult patients with CIC. Patients with CIC
were defined as having fewer than three spontaneous bowel movements per
week, and they also may have experienced recurrent straining, lumpy or
hard stools, and/or a sensation that they have not had a complete bowel
movement. Patients were randomized to receive 72 mcg of linaclotide once
per day, 145 mcg of linaclotide once per day, or placebo once per day
for 12 weeks. A 12-week CSBM Overall Responder was defined as a patient
who experienced at least three CSBMs per week and an increase of at
least one CSBM from baseline in the same week (Weekly Responder), and
achieved both of these measures for nine out of 12 weeks. A Durable
12-week CSBM Overall Responder comprises patients that were 12-week CSBM
Overall Responders and also met the Weekly Responder criteria for
at least three of the last four weeks. The 145 mcg dose was included as
a positive control and supported the validity of the trial for
evaluation of the 72 mcg dose.
About Chronic Idiopathic Constipation
Chronic idiopathic constipation (CIC) is a functional gastrointestinal
disorder in which individuals have infrequent bowel movements (less than
three times per week) and also may experience recurrent straining, lumpy
or hard stools, and/or a sensation that their bowels are not fully
empty. While estimates vary, as many as 35 million adult Americans may
suffer from CIC. Results derived from responses to a web-based survey
commissioned by Forest Pharmaceuticals, now a member of the Actavis
Group plc, and Ironwood suggest that only 12 percent of adult CIC
sufferers are medically diagnosed. There are few available prescription
treatment options for this condition.
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 Actavis 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 Almirall, S.A. for the treatment of adults
with moderate to severe IBS-C in Europe under the brand name CONSTELLA®.
Ironwood also has partnered with Astellas Pharma Inc. for development
and commercialization of linaclotide in Japan and with AstraZeneca for
development and commercialization in China.
LINZESS and CONSTELLA are trademarks owned by Ironwood Pharmaceuticals,
Inc. Any other trademarks referred to in this press release are the
property of their respective owners. All rights reserved.
Important Safety Information
WARNING: PEDIATRIC RISK
|
LINZESS is contraindicated in pediatric patients under 6 years
of age. In nonclinical studies, administration of a single,
clinically relevant adult oral dose of linaclotide caused deaths
due to dehydration in young juvenile mice. Use of LINZESS should
be avoided in pediatric patients 6 through 17 years of age. The
safety and efficacy of LINZESS has not been established in
pediatric patients under 18 years of age.
|
Contraindications
-
LINZESS is contraindicated in pediatric patients under 6 years of age.
-
LINZESS is contraindicated in patients with known or suspected
mechanical gastrointestinal obstruction.
Warnings and Precautions
Pediatric Risk
-
LINZESS is contraindicated in children under 6 years of age. The
safety and effectiveness of LINZESS in pediatric patients under 18
years of age have not been established. In neonatal mice, increased
fluid secretion as a consequence of GC-C agonism resulted in mortality
within the first 24 hours due to dehydration. Due to increased
intestinal expression of GC-C, children under 6 years of age may be
more likely than older children and adults to develop significant
diarrhea and its potentially serious consequences.
-
Use of LINZESS should be avoided in pediatric patients 6 through 17
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 through 17 years of age.
Diarrhea
-
Diarrhea was the most common adverse reaction of LINZESS-treated
patients in the pooled IBS-C and CIC double-blind placebo-controlled
trials. Severe diarrhea was reported in 2% of LINZESS-treated
patients. The incidence of diarrhea was similar in the IBS-C and CIC
populations.
-
Patients should be instructed to stop LINZESS if severe diarrhea
occurs and to contact their healthcare provider. The healthcare
provider should consider dose suspension and rehydration.
Adverse Reactions
-
In IBS-C clinical trials, the most common adverse reactions in
LINZESS-treated patients (incidence ≥2% and greater than placebo) were
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 clinical trials, the most common adverse reactions in
LINZESS-treated patients (incidence ≥2% and greater than placebo) were
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%).
Please see full Prescribing Information including Boxed Warning: http://www.frx.com/pi/linzess_pi.pdf
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ: IRWD) is focused on creating medicines
that make a difference for patients, building value to earn the
continued support of our fellow shareholders, and empowering our team to
passionately pursue excellence. We discovered, developed and are
commercializing linaclotide, which is approved in the United States and
a number of other countries. Our pipeline priorities include exploring
further opportunities for linaclotide, as well as leveraging our
therapeutic expertise in gastrointestinal disorders and our
pharmacologic expertise in guanylate cyclases to address patient needs
across the upper and lower gastrointestinal tract. Ironwood was founded
in 1998 and is headquartered in Cambridge, Mass. Connect with us at www.ironwoodpharma.com
or on Twitter at www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
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 results
of the 72 mcg linaclotide clinical program in CIC; the study's impact on
our future plans; the potential for 72 mcg linaclotide to provide
physicians with more treatment options and the benefits it may afford
adult CIC patients; the ability of our pipeline of guanylate cyclase-C
(GC-C) agonists to help patients with gastrointestinal dysfunction, and
our exploration thereof; and CIC symptoms, available treatments, the
rate of diagnosis and the size of the potential patient population. 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,
but are not limited to, the risks related to decisions related to
marketing authorization made by regulatory authorities; the risk that
the full data set from such clinical study is not available when we
currently anticipate it, is not consistent with this topline data or
does not adequately support marketing authorization approval of 72 mcg
linaclotide; the risk that the patient population is not as large as we
presently estimate; the risks related to the development of our pipeline
of GC-C agonists, including efficacy, safety and tolerability; and those
risks related to competition and future business decisions made by
Ironwood and its competitors or potential competitors. Applicable risks
also include those that are listed under the heading "Risk Factors" and
elsewhere in Ironwood's Quarterly Report on Form 10-Q for the quarter
ended June 30, 2015, in addition to the risk factors that are listed
from time to time in Ironwood's Annual Reports on Form 10‐K, Quarterly
Reports on Form 10‐Q and any other subsequent SEC filings. Ironwood
undertakes no obligation to update these forward-looking statements to
reflect events or circumstances occurring after this press release.
Except as otherwise noted, these forward-looking statements speak only
as of the date of this press release. All forward‐looking statements are
qualified in their entirety by this cautionary statement.
View source version on businesswire.com: http://www.businesswire.com/news/home/20151013006752/en/
Ironwood Pharmaceuticals, Inc.
Media Relations
Trista
Morrison, 617-374-5095
Director, Corporate Communications
[email protected]
or
Investor
Relations
Meredith Kaya, 617-374-5082
Director, Investor
Relations
[email protected]
Source: Ironwood Pharmaceuticals, Inc.
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