- All primary and secondary endpoints met with statistical
significance; companies expect to file for CFDA approval in early 2016 -
SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
AstraZeneca Pharmaceuticals Co., Ltd. and Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) announced today that top-line
data demonstrate linaclotide met all primary and secondary endpoints,
covering multiple abdominal and constipation symptoms, in a Phase III
clinical trial of adults with irritable bowel syndrome with constipation
(IBS-C). The trial was conducted primarily in China and the companies
intend to file in early 2016 for China Food and Drug Administration
(CFDA) approval to market linaclotide. Linaclotide is currently approved
in the United States for the treatment of adults with IBS-C or chronic
idiopathic constipation (CIC) and in a number of other countries for
adults with IBS-C.
"If approved by the CFDA, linaclotide would be the first prescription
treatment in China specifically for both male and female adults with
IBS-C, which is estimated to affect at least 13 million men and women in
this country," said Leon Wang, President of AstraZeneca China and Hong
Kong. "The successful completion of this Phase III clinical trial
confirms our belief that linaclotide may be able to help millions of
these patients suffering from abdominal pain, bloating and multiple
other abdominal and constipation symptoms associated with IBS-C."
"Linaclotide has now met all primary and secondary endpoints in all six
of its Phase III/IIIb trials. The efficacy and safety results seen in
this Phase III trial are consistent with the results of previous
linaclotide pivotal studies in adults with IBS-C and with our experience
in clinical practice, where nearly 700,000 unique IBS-C and CIC patients
in the U.S. have filled more than 2.7 million linaclotide prescriptions
since launch," said Mark Currie, Ph.D., chief scientific officer and
president of research and development at Ironwood. "We are making
progress toward our goal of bringing linaclotide to appropriate patients
around the world, and we continue to innovate with our development and
investigation of additional linaclotide indications and formulations
intended to address a broad spectrum of patient needs."
Top-line data from the Phase III trial indicate linaclotide-treated
patients showed statistically significant improvement compared to
placebo-treated patients for both co-primary endpoints. 60.0% of
linaclotide-treated patients were Abdominal Pain/Discomfort Responders,
compared to 48.8% of placebo-treated patients (p=0.001). 31.7% of
linaclotide-treated patients were IBS Degree of Relief Responders,
compared to 15.4% of placebo-treated patients (p < 0.0001).
Linaclotide-treated patients reported greater improvements in abdominal
pain than placebo-treated patients: these effects were evident in the
first week of treatment and continued to improve throughout the
treatment period, with the greatest decreases in abdominal pain seen at
week 12 of treatment (44% decrease for linaclotide compared to 34%
decrease for placebo).
Statistically significant improvements were achieved in all
pre-specified secondary endpoints in this trial, including abdominal
pain, abdominal discomfort, bloating, straining, frequency of complete
spontaneous bowel movements, frequency of spontaneous bowel movements
and stool consistency.
The most common adverse event reported in linaclotide-treated patients
was diarrhea (9.4% for linaclotide vs. 1.2% for placebo). Overall rates
of discontinuation due to adverse events were 1.7% for linaclotide vs.
1.4% for placebo, while discontinuation due to diarrhea was 0.7% for
linaclotide vs. 0.2% for placebo.
The randomized, double-blind, placebo-controlled Phase III clinical
trial randomized 839 adults with IBS-C in China, Australia, Canada, New
Zealand and the United States. Patients were randomized 1:1 to receive
either 290mcg of linaclotide, or placebo, for 12 weeks. The co-primary
endpoints of the trial were (i) 12-Week Abdominal Pain/Discomfort
Responder, which is defined as a patient who has at least a 30%
improvement in his/her abdominal pain or abdominal discomfort level for
at least half of the weeks in the 12-week treatment period, and (ii)
12-Week IBS Degree of Relief Responder, which is defined as a patient
who rates their IBS symptoms as being "considerably relieved" or
"completely relieved" for at least half of the weeks in the 12-week
treatment period. The primary endpoints used in this trial were similar
to those previously used to support approval of linaclotide in the
European Union. For comparison, results were also significant (33.7% for
linaclotide-treated patients versus 17.4% for placebo-treated patients,
nominal p < 0.0001) analyzing the data from this trial according to the
endpoint from the FDA guidance on IBS (patients reporting at least a 30%
reduction from baseline in abdominal pain and an increase of at least
one complete spontaneous bowel movement from baseline, all in the same
week for at least 6 out of 12 weeks).
Full results from the trial are expected to be submitted for
presentation at an upcoming medical congress.
AstraZeneca and Ironwood are jointly responsible for the development and
commercialization of linaclotide in China, with AstraZeneca primarily
responsible for local operational execution. Under the terms of the
collaboration, AstraZeneca made an upfront payment of $25 million to
Ironwood, and the two companies will share the net profits and losses
associated with linaclotide in China, with AstraZeneca carrying 55% of
each until a certain specified milestone is achieved, moving to a 50/50
split thereafter. Ironwood is also eligible for $125 million in
additional commercial milestone payments from AstraZeneca contingent on
the achievement of certain sales targets.
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), with nearly 700,000 unique patients in the U.S. having filled
more than 2.7 million linaclotide prescriptions since launch, according
to IMS Health. 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.
About AstraZeneca Pharmaceuticals Co. Ltd.
AstraZeneca is a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of cardiovascular,
metabolic, respiratory, inflammation, autoimmune, oncology, infection
and neuroscience diseases. AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
For more information please visit: www.astrazeneca.com
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.
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.
This press release contains forward looking statements. Investors are
cautioned not to place undue reliance on these forward‐looking
statements, which include, among other things, statements about the
top-line assessment of the data from the Phase III clinical trial of
linaclotide in adults with IBS-C and the plans for further analysis; the
development and regulatory plans for linaclotide in China, and the
timing of those decisions; the design of the Phase III trial and its
impact on the results thereof; the design and possible benefits of
linaclotide and its potential as a treatment for adult men and women
IBS-C patients in China; IBS-C symptoms and the causes of such symptoms,
as well as available treatments, prevalence and unmet need; market size,
growth and opportunity, and potential demand for linaclotide in China;
and the potential for Ironwood to receive sales-related milestones from
AstraZeneca. 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 risk that Ironwood
and AstraZeneca are unable to effectively or timely execute on the
development and regulatory plan for linaclotide, or do so in a
cost-effective manner; the risk that findings from the completed
linaclotide clinical trials may not be predictive of the product's
performance, if it is commercialized; the risk that unfavorable findings
may arise from new clinical data or additional analyses of existing
clinical data; those related to the efficacy, safety and tolerability of
linaclotide; those related to decisions made by regulatory authorities
and the timing of those decisions; the commercial potential of
linaclotide in China; the risk that Ironwood and AstraZeneca may never
get sufficient patent protection for linaclotide in China; those related
to intellectual property rights of competitors or potential competitors;
the risk that the patient population is not as presently estimated; the
risks presented by future business decisions made by Ironwood,
AstraZeneca and their competitors or potential competitors; and the risk
that Ironwood or AstraZeneca terminates all or part of the collaboration
arrangement. Applicable risks also include those that are listed in
Ironwood's Quarterly Report on Form 10‐Q for the quarter ended March 31,
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 subsequent SEC filings. Neither Ironwood nor AstraZeneca
undertakes any obligation to update these forward‐looking statements to
reflect events or circumstances occurring after this press release.
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/20150708005179/en/
Ironwood Pharmaceuticals, Inc.
Media Relations:
Trista
Morrison, 617-374-5095
tmorrison@ironwoodpharma.com
or
Investor
Relations:
Meredith Kaya, 617-374-5082
mkaya@ironwoodpharma.com
or
AstraZeneca China
Media
Relations:
Chris Wang, 86-21-6070 1073
chris.wang@astrazeneca.com
Source: Ironwood Pharmaceuticals, Inc. and AstraZeneca Pharmaceuticals Co., Ltd.
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