- 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
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
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
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
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.
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.
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
Senior Director, Investor Relations and Corporate Communications
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