Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) announced today that top-line
data from an exploratory Phase IIa clinical study indicate IW-3718
improved heartburn and certain other symptoms associated with refractory
gastroesophageal reflux disease (GERD). Based on these initial data,
Ironwood intends to advance IW-3718 into a dose-ranging Phase IIb study.
Refractory GERD, which affects an estimated 8 million Americans, is
characterized by the chronic presence of symptoms such as heartburn
despite treatment with a proton pump inhibitor (PPI) to suppress stomach
acid. Research suggests some refractory GERD patients may experience
reflux of bile from the intestine into the stomach and esophagus.
IW-3718 is a novel formulation of a bile acid sequestrant designed to
bind over an extended period of time to bile that refluxes into the
stomach and upper small intestine, potentially providing symptomatic
relief in refractory GERD.
“This study explored the hypothesis that some refractory GERD patients
experience bile reflux into the esophagus, and our initial data confirm
that hypothesis. Approximately two-thirds or 33 of the 52 patients who
underwent bile reflux monitoring tested positive for bile reflux into
the esophagus during the pretreatment period of the study,” said Mark
Currie, Ph.D., senior vice president, chief scientific officer, and
president of research and development at Ironwood. “Importantly, the
subgroup of patients in this study who tested positive for bile reflux
and received IW-3718 demonstrated encouraging improvements in relief of
heartburn and certain other upper gastrointestinal symptoms often
associated with refractory GERD, when compared to patients receiving
placebo.”
Heartburn was the most severe and most frequent symptom experienced by
patients before starting study treatment. Average baseline heartburn
severity among study participants was 3.5 on a 10-point scale, with 0
representing no heartburn and 10 representing very severe heartburn. The
improvement in heartburn severity for IW-3718-treated patients was 1.7
points in the overall trial population and 2.1 points in the subgroup of
patients who tested positive for bile reflux (versus 1.2 points and 1.1
points, respectively, for the placebo-treated groups in each
comparison). In terms of frequency, patients entering the trial reported
that only 13.7% of their days were free of heartburn. The percentage of
heartburn-free days for IW-3718-treated patients increased by 30.3% in
the overall trial population and 34.6% in the bile reflux-positive
subgroup (versus 24.7% and 23.6%, respectively, for the placebo-treated
groups in each analysis). Patients receiving IW-3718 also demonstrated
encouraging improvements in regurgitation and in some upper GI symptoms
that are often associated with GERD, including epigastric burning, early
fullness and post-prandial fullness. Symptom improvements were greatest
in the bile reflux-positive subgroup. Additionally, 45.7% and 56.3% of
IW-3718-treated patients in the overall trial population and in the bile
reflux-positive subgroup, respectively, were responders regarding degree
of relief of overall GERD symptoms (versus 27.7% and 29.4%,
respectively, for the placebo-treated groups in each analysis). Certain
upper GI symptoms that did not appear to be impacted by treatment
included nausea, epigastric pain and bloating. IW-3718 was generally
well-tolerated with the most common adverse event being constipation.
The randomized, double-blind, placebo-controlled, multi-site, Phase IIa
study enrolled 93 patients with a confirmed diagnosis of GERD who were
taking a PPI and continuing to experience frequent GERD symptoms,
including heartburn at least four days per week. The trial included a
two-week pretreatment period during which baseline symptoms were
assessed via an electronic diary, followed by a randomization period in
which patients had the option to undergo 24-hour Bilitec® and pH
monitoring to assess the extent of esophageal exposure to bile and acid
reflux. Patients were randomized to receive either 1,000 mg of IW-3718
or placebo twice-daily for four weeks. Patients continued to take their
PPI during the pretreatment, randomization and treatment periods. The
exploratory study evaluated a number of GERD-related symptoms rather
than specifying a primary endpoint, and as such was not powered to
establish the statistical significance of a particular endpoint. Data
presented for heartburn severity and heartburn-free days reflect change
from baseline to week four. For the responder analysis, responders
regarding degree of relief of overall GERD symptoms were defined as
patients who reported scores of 1 (completely relieved) or 2
(considerably relieved) on a seven-point scale for at least two out of
four weeks in the treatment period, or who reported scores of 1, 2 or 3
(somewhat relieved) for all four weeks.
Ironwood plans to further analyze data from the trial and present the
findings at an upcoming medical meeting.
About IW-3718
IW-3718 is a novel, gastric retentive formulation of a bile acid
sequestrant, developed by Ironwood using the proprietary Acuform® drug
delivery technology licensed from Depomed, Inc. IW-3718 is designed to
deliver the bile acid sequestrant to the desired sites of action –
specifically the stomach and duodenum (upper small intestine) – over an
extended period of time. Data from non-clinical studies support the
extended release profile of IW-3718.
About Refractory Gastroesophageal Reflux Disease (GERD)
An estimated 8 million Americans suffer from refractory gastroesophageal
reflux disease (GERD), experiencing continued symptoms such as heartburn
and regurgitation despite receiving the current standard of care
treatment with a proton pump inhibitor (PPI) to suppress stomach acid
production. There are a limited number of FDA-approved treatment options
for these patients. Research suggests reflux of bile from the intestine
into the stomach and esophagus may play a role in the ongoing symptoms
of refractory GERD patients.
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.
Any 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, including, but not limited to, statements about our top-line
assessment of the data from the Phase IIa clinical trial of IW-3718 in
refractory GERD and our plans for further analysis; our development
plans for IW-3718, including the planned advancement of IW-3718 into a
dose-ranging Phase IIb study; the design of the Phase IIa trial and its
impact on the results thereof; the design and possible benefits
of IW-3718 and its potential as a treatment for refractory GERD; and
refractory GERD symptoms and the causes of such symptoms, as well as
available treatments, prevalence and unmet need. 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 we are unable to effectively execute on our
clinical program for IW-3718 and do so in a timely and cost-effective
manner; those risks related to pre-clinical and clinical development;
the risk that findings from our completed nonclinical studies may not be
replicated in later clinical trials, or that our clinical trials may not
be predictive of the results we may obtain in later-stage clinical
trials; 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 IW-3718; those related to
decisions made by regulatory authorities; the risk that we may never get
sufficient patent protection for IW-3718; those related to intellectual
property rights of competitors or potential competitors; the risk that
the patient population is not as we presently estimate; and the risks
presented by future business decisions made by us, our partners and our
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 September
30, 2014, 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.
Copyright Business Wire 2015