TOKYO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 29, 2017--
Pharma Inc. (TSE:4503) and Ironwood
Pharmaceuticals, Inc. (NASDAQ:IRWD) announced today top-line results
indicating that the Phase III clinical trial of linaclotide conducted in
Japan in adults with chronic constipation (CC) met its primary endpoint.
Linaclotide is approved in Japan as the first prescription treatment for
adults with irritable bowel syndrome with constipation (IBS-C).
Linaclotide is currently approved in the United States for the treatment
of adults with IBS-C or chronic idiopathic constipation (CIC). It is
also approved for adults with IBS-C or CIC in more than 30 other
countries. Patients in the Phase III CC trial in Japan continue to
receive open-label linaclotide for an additional 52 weeks; the blinded
efficacy data coupled with these open-label safety data are expected to
form the basis for regulatory review and potential approval for this
indication in Japan.
“I am really pleased to receive the positive top-line results from the
Phase III chronic constipation trial. If approved, Astellas expects
linaclotide to provide a new therapeutic option for patients suffering
from this condition, in addition to IBS-C, for which linaclotide has
already obtained marketing approval in Japan,” said Bernhardt G. Zeiher,
M.D., President, Development at Astellas Group.
“Today’s positive Phase III results for linaclotide in chronic
constipation mark the ninth Phase III/IIIb clinical trial in which
linaclotide has met its primary endpoints, once again demonstrating
consistent results in clinical trials across two indications, evaluating
multiple doses and conducted in multiple countries,” said Mark Currie,
Ph.D., Chief Scientific Officer and President of Research and
Development at Ironwood. “We look forward to working with Astellas to
support the launch of linaclotide in Japan for adults with IBS-C and to
advance it for CC.”
The double-blind, placebo-controlled Phase III clinical trial randomized
186 adults with CC in Japan to receive either 500 mcg of linaclotide or
placebo for 4 weeks (1:1 ratio). The top-line trial results indicate
that linaclotide-treated patients showed statistically significant
improvement compared to placebo-treated patients for the primary
endpoint, change from baseline in mean spontaneous bowel movement
frequency at Week 1. The most common adverse event reported in this
trial was diarrhea. All cases of diarrhea were characterized as mild or
moderate in severity.
Further detailed results from the Phase III trial are expected to be
presented at an upcoming scientific meeting.
INDICATIONS AND USAGE (UNITED STATES)
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 (UNITED STATES)
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 has not been established in patients less
than 18 years of age.
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 Precautions
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 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 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
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 clinical trial of a 72 mcg dose:
diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).
Please see full Prescribing Information: http://www.allergan.com/assets/pdf/linzess_pi
Linaclotide is a guanylate cyclase‐C (GC‐C) agonist that is structurally
related to the naturally occurring peptides, guanylin and uroguanylin.
Linaclotide 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), with
nearly 1.5 million unique patients in the United States having filled
nearly 7 million linaclotide prescriptions since launch, according
to IMS Health. Linaclotide is marketed by Allergan for the treatment of
adults with moderate to severe IBS-C in Europe under the brand name
CONSTELLA®, and Ironwood’s partner Astellas received approval
of linaclotide in Japan under the brand name LINZESS® for the
treatment of adults with IBS-C. Ironwood also has partnered with
AstraZeneca for development and commercialization of linaclotide
in China, Hong Kong and Macau.
Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to
improving the health of people around the world through the provision of
innovative and reliable pharmaceutical products. We focus on Urology,
Oncology, Immunology, Nephrology and Neuroscience as prioritized
therapeutic areas while advancing new therapeutic areas and discovery
research leveraging new technologies/modalities. We are also creating
new value by combining internal capabilities and external expertise in
the medical/healthcare business. Astellas is on the forefront of
healthcare change to turn innovative science into value for patients.
For more information, please visit our website at www.astellas.com/en.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ: IRWD) is a commercial biotechnology
company focused on creating medicines that make a difference for
patients, building value for our fellow shareholders, and empowering our
passionate team. We are commercializing two innovative primary care
products: linaclotide, the U.S. branded prescription market leader for
adults with irritable bowel syndrome with constipation (IBS-C) or
chronic idiopathic constipation (CIC), and lesinurad, which is approved
to be taken with a xanthine oxidase inhibitor (XOI) for the treatment of
hyperuricemia associated with uncontrolled gout. We are also advancing a
pipeline of internally and externally generated innovative product
candidates in areas of significant unmet need, including uncontrolled
gastroesophageal reflux disease and vascular and fibrotic diseases.
Ironwood was founded in 1998 and is headquartered in Cambridge, Mass.
For more information, please visit www.ironwoodpharma.com
information that may be important to investors will be routinely posted
in both these locations.
Ironwood Cautionary Notes
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about the launch of linaclotide in
Japan for adults with IBS-C; the basis for regulatory review and
potential approval for linaclotide in Japan in adults with CC; the
potential benefits of linaclotide; and disclosure of data from the Phase
III trial, and the timing thereof. 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 the
effectiveness of commercialization efforts by us and our partners; those
related to preclinical and clinical development, manufacturing and
formulation development; the risk that findings from our completed
nonclinical and clinical studies may not be replicated in later studies;
efficacy, safety and tolerability of linaclotide; decisions by
regulatory authorities; the risk that we may never get sufficient patent
protection for linaclotide or that we are not able to successfully
protect such patents; developments in the intellectual property
landscape; challenges from and rights of competitors or potential
competitors; and the risks listed under the heading "Risk Factors" and
elsewhere in Ironwood's Quarterly Report on Form 10-Q for the quarter
ended September 30, 2016, and in our subsequent SEC filings. These
forward-looking statements (except as otherwise noted) speak only as of
the date of this press release, and Ironwood undertakes no obligation to
update these forward-looking statements.
Astellas Cautionary Notes
The safety and efficacy of the agents discussed herein are under
investigation and have not been established. There is no guarantee that
the agents will receive regulatory approval and become commercially
available for uses being investigated. Information about pharmaceutical
products (including products currently in development) which is included
in this press release is not intended to constitute an advertisement or
In this press release, statements made with respect to current plans,
estimates, strategies and beliefs and other statements that are not
historical facts are forward-looking statements about the future
performance of Astellas. These statements are based on management’s
current assumptions and beliefs in light of the information currently
available to it and involve known and unknown risks and uncertainties. A
number of factors could cause actual results to differ materially from
those discussed in the forward-looking statements. Such factors include,
but are not limited to: (i) changes in general economic conditions and
in laws and regulations, relating to pharmaceutical markets, (ii)
currency exchange rate fluctuations, (iii) delays in new product
launches, (iv) the inability of Astellas to market existing and new
products effectively, (v) the inability of Astellas to continue to
effectively research and develop products accepted by customers in
highly competitive markets, and (vi) infringements of Astellas’
intellectual property rights by third parties.
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
View source version on businesswire.com: http://www.businesswire.com/news/home/20170129005019/en/
Source: Ironwood Pharmaceuticals, Inc. & Astellas Pharma Inc.
Ironwood Pharmaceuticals, Inc.
Meredith Kaya, 617-374-5082
Media Relations: +81- 3-3244-3201