- IW-3718 1500 mg demonstrated a significant reduction in heartburn
severity in patients with uncontrolled GERD -
- Greater than 50% of patients treated with IW-3718 1500 mg achieved
a clinically meaningful reduction in heartburn severity -
- IW-3718 1500 mg also showed reductions in regurgitation frequency -
- Ironwood expects to advance IW-3718 into Phase III -
- Conference call scheduled today at 8:30 a.m. ET -
CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD), a commercial biotechnology
company, announced positive top-line data from a Phase IIb clinical
trial evaluating IW-3718 in adult patients with uncontrolled
gastroesophageal reflux disease (GERD). The trial met its primary
endpoint, indicating that twice-daily, oral dosing of IW-3718 1500 mg
plus a proton pump inhibitor (PPI) significantly reduced heartburn
severity in patients with uncontrolled GERD compared to patients treated
with a PPI alone. Further, more than half of patients treated with
IW-3718 1500 mg plus a PPI achieved a clinically meaningful reduction in
heartburn severity. IW-3718 1500 mg was well tolerated in the trial.
Ironwood plans to have end of Phase II meetings with the U.S. Food and
Drug Administration (FDA), after which the company expects to advance
IW-3718 1500 mg into Phase III development in the second half of 2018.
Uncontrolled GERD is a chronic condition affecting an estimated 10
million Americans who continue to suffer from symptoms such as heartburn
and regurgitation despite receiving treatment with PPIs - the current
standard of care - to suppress acid produced in the stomach. Ironwood's
clinical research has demonstrated that reflux of bile from the
intestine into the stomach and esophagus plays a key role in the ongoing
symptoms of uncontrolled GERD. IW-3718 is a novel formulation of a bile
acid sequestrant designed to release in the stomach over an extended
period of time, bind to bile that refluxes into the stomach, and
potentially provide symptomatic relief in uncontrolled GERD.
"Millions of patients with GERD globally are significantly impacted by
frequent and bothersome heartburn and regurgitation symptoms despite
diligently taking their PPIs. They are seeking relief, asking for new
treatment options and we really have nothing to offer them," said
Michael Vaezi, M.D., Ph.D., professor of medicine, division of
gastroenterology and hepatology, director of the Center for Swallowing
and Esophageal Disorders at Vanderbilt University Medical Center and an
investigator for the study. "The data from this trial are encouraging,
as they provide strong evidence that bile plays a key role in
uncontrolled GERD and that IW-3718 may bring a much-needed new approach
to treating these patients."
Data from the Phase IIb trial showed a dose response across the primary
and key secondary endpoints, with the most pronounced response observed
at the highest dose of IW-3718 studied (1500 mg). Top-line data were as
follows:
-
Percent Change from Baseline to Week 8 in Weekly Heartburn Severity
(primary endpoint): patients treated with IW-3718 1500 mg plus a
PPI showed a mean decrease of 58.0% from baseline in heartburn
severity compared to 46.0% in patients treated with a PPI alone (p =
0.04).
-
Clinically Meaningful Degree of Improvement in Weekly Heartburn
Severity: a 45% reduction in weekly heartburn severity was
determined to be clinically meaningful for patients in this study
based on patient-reported outcome measures.
-
Heartburn Responder: a heartburn responder was defined as a
patient who experienced at least a 45% reduction from baseline in
heartburn severity for at least four out of eight weeks, including at
least one of the last two weeks. 52.9% of patients treated with
IW-3718 1500 mg plus a PPI were heartburn responders, compared to
37.1% of patients treated with a PPI alone.
-
Percent Change from Baseline to Week 8 in Weekly Regurgitation
Frequency: patients treated with IW-3718 1500 mg plus a PPI showed
a mean decrease of 55.4% from baseline in regurgitation frequency
compared to 37.9% in patients treated with a PPI alone (among patients
with baseline regurgitation; p = 0.01).
There were no treatment-related serious adverse events reported with
IW-3718 1500 mg. The most common adverse event reported overall was
constipation, which was reported in 7.4% of patients on IW-3718 1500 mg
plus a PPI (n=5) compared to 7.1% of patients on a PPI alone (n=5). All
constipation adverse events reported were mild or moderate in severity.
Discontinuation rates due to adverse events were less than 5% and
similar across treatment groups.
"The results from this trial, demonstrating encouraging improvements in
heartburn severity and regurgitation, appear to validate our approach of
targeting bile acid reflux in patients with uncontrolled GERD in
addition to suppressing acid with PPIs," said Mark Currie, Ph.D., senior
vice president, chief scientific officer, and president of research and
development at Ironwood. "These data were consistent and robust across
key endpoints, and reinforce our belief that IW-3718 may lead to
meaningful symptom relief for patients with uncontrolled GERD."
Ironwood intends to present additional data from the Phase IIb clinical
trial at an upcoming scientific meeting and/or via peer-reviewed
publications.
IW-3718 is wholly-owned by Ironwood. Ironwood has existing patents and
pending patent applications for IW-3718 that are expected to provide
patent coverage into the mid-2030s.
Conference Call Information
Ironwood will host a conference call and webcast at 8:30 a.m. Eastern
Time on Thursday, July 20, 2017, to discuss the top-line results of the
IW-3718 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
58702323. 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 July 20, 2017 running through 11:59 p.m. Eastern Time
on July 27, 2017. To listen to the replay, dial (855) 859-2056 (U.S. and
Canada) or (404) 537-3406 (international) using conference ID number
58702323. The archived webcast will be available on Ironwood's website
for 14 days beginning approximately one hour after the call has
completed.
Phase IIb Trial Design
The randomized, double-blind, placebo-controlled Phase IIb clinical
trial enrolled 282 adult patients with GERD (including 276 adult
patients with baseline regurgitation), confirmed by endoscopy, who were
taking a PPI and continuing to experience GERD symptoms, including
heartburn and regurgitation, at least four days per week during the
previous eight weeks. The trial included a two-week pretreatment period,
during which baseline symptoms were assessed via an electronic diary.
Patients were then randomly assigned to receive either placebo or one of
three doses of IW-3718 (500 mg, 1,000 mg or 1,500 mg) twice daily for
eight weeks, in addition to their daily PPI therapy. The primary
efficacy endpoint was percent change in weekly heartburn severity from
baseline to week 8. Additionally, a heartburn responder endpoint was
defined based on a clinically meaningful degree of improvement derived
for the uncontrolled GERD population from patient reported outcome
measures collected in the study. No adjustments were made for
multiplicity; p-values were reported as nominal.
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 formulation technology licensed from Depomed, Inc. IW-3718 is
designed to deliver the bile acid sequestrant to the stomach over an
extended period of time where it is positioned to intercept bile before
it reaches the esophagus. Data from non-clinical and clinical studies
collectively support the extended release and gastric-retentive profile
of IW-3718. Ironwood has existing patents and pending patent
applications for IW-3718 that are expected to provide patent coverage
into the mid-2030s.
About Uncontrolled Gastroesophageal Reflux Disease (GERD)
An estimated 10 million adult Americans and more than 60 million adult
patients globally suffer from uncontrolled gastroesophageal reflux
disease (GERD), meaning they continue to experience symptoms such as
heartburn and regurgitation despite receiving treatment with a proton
pump inhibitor (PPI). While PPIs suppress production of stomach acid,
Ironwood's clinical research demonstrates that reflux of bile from the
intestine into the stomach and esophagus plays a key role in the ongoing
symptoms of uncontrolled GERD. FDA-approved treatment options for these
patients are limited.
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
or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
ACUFORM® is a registered trademark of Depomed, Inc.
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 IW-3718; the development,
regulatory and commercialization plans for IW-3718, and the timing
thereof, including further investigation and advancement of IW-3718,
engaging with the FDA, advancing IW-3718 into Phase III development and
commercializing IW-3718 within and outside the U.S.; the design of the
Phase IIb trial and its impact on the results thereof, as well as the
results and their validation of our approach to targeting bile acid
reflux in patients with uncontrolled GERD and expectations relating to
replication in Phase III; the timing of presentation of additional
IW-3718 Phase IIb data; the design, potential indications for, and
possible benefits of IW-3718 and its potential as a treatment for
patients with uncontrolled GERD; the potential for patient adherence to
IW-3718; the level of competition in the uncontrolled GERD space;
physicians' willingness to adopt and the potential for broad payer
access and reimbursement; prevalence and unmet need; market size, growth
and opportunity, including peak sales and potential demand for IW-3718
in the U.S.; and the strength of the intellectual property protection
for IW-3718. 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 IW-3718; the risk that the therapeutic
opportunities for IW-3718 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 IW-3718 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 March 31, 2017, 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170720005395/en/
Ironwood Pharmaceuticals, Inc.
Meredith Kaya, 617-374-5082
Senior
Director, Investor Relations and Corporate Communications
mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc.
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