Data also support potential for broad opportunity to treat
additional GI indications associated with abdominal pain
Companies separately announced Phase IIb data with linaclotide
colonic release-1 (CR1) for IBS-C
Ironwood to host conference call today at 8:30 a.m. Eastern Time
CAMBRIDGE, Mass. & DUBLIN--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ:IRWD) and Allergan
plc (NYSE:AGN) announced today topline data from a Phase IIb
clinical trial evaluating an investigational linaclotide colonic
release-2 (CR2) formulation in adult patients with irritable bowel
syndrome with constipation (IBS-C). The data showed that CR2, as
intended, numerically improved abdominal pain and other abdominal
symptoms, such as bloating and discomfort, relative to placebo, with no
apparent effect on bowel movement function. These findings support
further investigation of CR2 in specific GI indications where patients
experience abdominal pain but are not necessarily constipated, such as
IBS-Mixed, IBS with diarrhea, ulcerative colitis and diverticulitis. The
companies plan to engage with the U.S. Food and Drug Administration
(FDA) to discuss next steps for advancing CR2 into a Phase IIb
dose-ranging clinical trial in patients with non-constipation subtypes
of IBS.
"There is increasing research into the mechanisms underlying pain and
other abdominal symptoms in GI disorders, including IBS, as well as
research highlighting the hypersensitivity of pain-sensing nerves in the
lower GI tract in many patients suffering from these conditions," said
Brennan Spiegel, director of Health Services Research at Cedars-Sinai
Health System. "We currently have a limited number of treatment options
for these patients, and a medicine that could address abdominal pain
without impacting bowel function could represent a real advancement in
care."
Linaclotide is currently FDA-approved and available in an immediate
release (IR) formulation, LINZESS®, for the treatment of
adults with IBS-C or chronic idiopathic constipation (CIC). Linaclotide
is thought to work in two ways, based on non-clinical studies: by
decreasing the activity of pain-sensing nerves and by increasing fluid
secretion into the intestine. Linaclotide CR2 is designed to provide
targeted delivery of linaclotide to the colon, where the majority of the
abdominal pain associated with IBS-C is believed to originate. This
clinical trial was designed to evaluate whether CR2 could further
decrease the activity of key pain-sensing nerves in the colon with a
minimal effect on fluid secretion. Ironwood and Allergan also announced
topline results from the same Phase IIb trial with a second formulation,
linaclotide colonic release-1 (CR1), in a separate press release issued
today.
The double-blind, placebo-controlled, dose-ranging Phase IIb trial
randomized 532 adult patients with IBS-C into one of eight possible
treatment arms. This trial was exploratory in nature and comparisons to
placebo were evaluated using nominal p-values. In the trial, the average
weekly change in Bristol Stool Form Scale (BSFS) scores and frequency of
complete spontaneous bowel movements (CSBM) from baseline to week 12
were comparable for CR2 and placebo (BSFS: 1.0 - 1.15 for CR2 compared
to 0.94 for placebo on a 7-point scale; CSBM: 0.87 - 1.28 for CR2
compared to 1.11 for placebo), indicating no apparent effect on bowel
movement function in this study. In contrast, the average weekly change
in abdominal pain from baseline to week 12 ranged from -1.63 to -1.83
across the CR2 dose range studied versus -1.37 for placebo, using an
11-point scale. Reduction from baseline at week 12 in abdominal pain was
-33.8% to -36.6% for the CR2 doses compared to -26.2% for placebo.
Together these data suggest the potential for CR2 to reduce abdominal
pain in GI indications not associated with constipation.
The most common adverse event in CR2 patients in this trial was upper
respiratory tract infection/nasopharyngitis, which was reported in 3% of
CR2-treated patients and 4.5% of placebo-treated patients. The rate of
diarrhea reported in the trial ranged from 0%-3% for CR2-treated
patients compared to 1.5% for placebo.
Additional data from the Phase IIb trial are expected to be shared at
upcoming scientific meetings and via peer-reviewed publications.
"With the linaclotide colonic release program, our intent was to dial up
or down the two components of the linaclotide mechanism of action - the
effect on pain-sensing nerves and the effect on fluid secretion - by
varying where the drug is delivered," said Mark Currie, Ph.D., chief
scientific officer and president of research and development at
Ironwood. "These initial data support our hypothesis that delivery in
the proximal ileum and colon could allow us to better isolate
linaclotide's ability to decrease the activity of pain-sensing nerves in
the intestine, and we look forward to advancing CR2 from IBS-C into GI
indications where patients experience abdominal pain but not
constipation."
"The linaclotide colonic release program is a testament to the
pioneering pharmacology work done by Mark Currie and the Ironwood team,
which led to linaclotide being the first and only FDA-approved guanylate
cyclase-C agonist, and is now continuing to raise the bar for innovation
in this field," said David Nicholson, Ph.D., chief R&D officer at
Allergan. "The encouraging data from this study warrant further
investigation of CR2 and its potential to benefit the additional 20-25
million patients estimated to suffer from non-constipation subtypes of
IBS."
Ironwood and Allergan are pursuing patent protection for CR1 and CR2
that, if issued, is expected to provide patent coverage into the
mid-2030s.
Ironwood Conference Call Today at 8:30 a.m. ET:
Ironwood will host a conference call and webcast at 8:30 a.m. Eastern
Time on Thursday, December 22, to discuss the results of the linaclotide
colonic release Phase IIb clinical trial. Individuals interested in
participating in the call should dial (877) 643-7155 (U.S. and
Canada) or (914) 495-8552 (international) using conference ID number
43363931. To access the webcast, please visit the Investors section of
Ironwood's website at www.ironwoodpharma.com
at least 15 minutes prior to the start of the call to ensure adequate
time for any software downloads that may be required. The call will be
available for replay via telephone starting at approximately 11:30 a.m.
Eastern Time, on December 22, running through 11:59 p.m. Eastern Time on
December 29, 2016. To listen to the replay, dial (855) 859-2056 (U.S.
and Canada) or (404) 537-3406 (international) using conference ID number
43363931. The archived webcast will be available on Ironwood's website
for 14 days beginning approximately one hour after the call has
completed.
Study Design
Patients in the double-blind, placebo-controlled, dose-ranging Phase IIb
clinical trial were randomized to one of eight groups: one group
received placebo, one group received linaclotide 290 mcg (approved
formulation), three groups received various doses of linaclotide CR1 (30
mcg, 100 mcg or 300 mcg), and three groups received various doses of
linaclotide CR2 (30 mcg, 100 mcg or 300 mcg). The 290 mcg approved
formulation was included as a reference group for this study. The trial
was designed to evaluate the safety and efficacy of each linaclotide
colonic release dose and formulation relative to placebo; the
statistical power was based on a linear dose response. Additional
objectives included assessing how the two colonic release formulations
compared to each other and to the approved 290 mcg formulation of
linaclotide. All doses were administered orally, once daily for 12 weeks.
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 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'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.
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 advancing a pipeline of innovative medicines in
areas of significant unmet need, including irritable bowel syndrome with
constipation (IBS-C)/chronic idiopathic constipation (CIC), uncontrolled
gout, refractory gastroesophageal reflux disease, and vascular and
fibrotic diseases. We discovered, developed and are commercializing
linaclotide, the U.S. branded prescription market leader in the
IBS-C/CIC category, and we are applying our proven R&D and commercial
capabilities to advance multiple internally-developed and
externally-accessed product opportunities. Ironwood was founded in 1998
and is headquartered in Cambridge, Mass. For more information, please
visit www.ironwoodpharma.com or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold,
global pharmaceutical company and a leader in a new industry model -
Growth Pharma. Allergan is focused on developing, manufacturing and
commercializing branded pharmaceuticals, devices and biologic products
for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class
products for the central nervous system, eye care, medical aesthetics
and dermatology, gastroenterology, women's health, urology and
anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, the Company's R&D model,
which defines our approach to identifying and developing game-changing
ideas and innovation for better patient care. This approach has led
to Allergan building one of the broadest development pipelines in the
pharmaceutical industry with 65+ mid-to-late stage pipeline programs in
development.
Our Company's success is powered by our more than 16,000 global
colleagues' commitment to being Bold for Life. Together, we build
bridges, power ideas, act fast and drive results for our customers and
patients around the world by always doing what is right.
With 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.
For more information, visit Allergan's website at www.Allergan.com.
Forward-Looking Statement
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about the topline assessment of the
data from the Phase IIb clinical trial of CR2; the development and
regulatory plans for CR2, and the timing thereof, including further
investigation and advancement of CR2, engaging with the FDA and
advancing CR2 into a Phase IIb dose-ranging clinical trial; the design
of the Phase IIb trial and its impact on the results thereof; the timing
of additional Phase IIb data; the potential indications for, and
benefits of, CR2; the design and possible benefits of CR2 and its
potential as a treatment for patients; prevalence and unmet need;
market size, growth and opportunity, and potential demand for CR2 in the
U.S.; and the strength of the intellectual property protection 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 linaclotide; the risk that the therapeutic
opportunities for the CR formulations are not as we expect; decisions by
regulatory authorities; those risks related to competition and future
business decisions made by us and our competitors or potential
competitors; the risk that we may never get sufficient patent protection
for linaclotide and our product candidates or that we are not able to
successfully protect such patents; developments in the intellectual
property landscape; 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, Allergan's Annual Report on Form
10-K for the year ended December 31, 2015 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.
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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20161222005169/en/
Allergan
Mark Marmur, 862-261-7558
Global Corporate
Media Relations
mark.marmur@allergan.com
or
Fran
DeSena, 201-427-8762
US Product Relations
fran.desena@allergan.com
or
Lisa
DeFrancesco, 862-261-7152
Investor Relations
lisa.defrancesco@allergan.com
or
Ironwood
Pharmaceuticals, Inc.
Trista Morrison, 617-374-5095
Director,
Corporate Communications
tmorrison@ironwoodpharma.com
or
Meredith
Kaya, 617-374-5082
Director, Investor Relations
mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc. and Allergan
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