Effects of a Gastric-Retentive Extended-Release Bile Acid Sequestrant on Esophageal Erosions in Patients With Persistent GERD: Exploratory Analysis From a Phase 2B Study of IW-3718

Introduction: Gastroesophageal reflux disease (GERD) is a chronic medical disorder, characterized by symptoms and/or complications resulting from the reflux of gastric contents into the esophagus. Approximately 30% of patients with GERD have erosive esophagitis (EE). IW-3718 is an investigational gastricretentive extended-release bile acid sequestrant designed to improve GERD symptoms by binding bile acids in the stomach and upper duodenum. The effects of IW-3718 on esophageal erosions were analyzed in a subgroup of patients with evidence of EE who participated in a recent phase 2b study of IW-3718 in patients with persistent GERD. Persistent GERD patients continue to suffer heartburn and regurgitation symptoms despite ongoing proton-pump inhibitor (PPI) treatment. Methods: Patients with a diagnosis of GERD, taking a daily labeled dose of PPI, and experiencing GERD symptoms ≥4 days per week were randomized to receive IW-3718 (500 mg, 1000 mg, and 1500 mg) or placebo twice daily for 8 weeks. Patients continued their PPI dose regimen throughout the study. All patients underwent esophagogastroduodenoscopy (EGD) at baseline and study investigators graded patients’ EE according to the Los Angeles classification scale. Patients with EE Grade C or D at baseline were required to have a repeat EGD at Week 8 (end of study) and their EE grading was compared to baseline. Proportions of patients showing improved EE grade were compared (IW-3718 vs placebo) using a 2-sided Fisher’s exact test. Results: Of 147 randomized patients with evidence of EE, 11 had Grade C or D erosions at baseline; 10 of these patients (7 IW-3718; 3 placebo) had Week-8 EGD results. In addition, 2 patients (1 IW-3718; 1 placebo) with lower baseline grading also underwent a repeat EGD. Of the 8 IW-3718-treated patients with Week-8 EGD results, 7 (87.5%) showed an improved EE grade and 1 was unchanged; in the placebo group 1 (25.0%) improved from C to B, and 3 were unchanged or worsened (see Table) (P=0.07, IW-3718 [all doses combined] vs placebo). Conclusion: These are the first available clinical results examining the effect of a novel extended-release formulation of a gastric-retentive, bile acid sequestrant on reflux-induced EE. Despite the limitations of low patient numbers and very limited data for patients with milder EE, preliminary data from this randomized, double-blind controlled study suggest IW-3718 did not exacerbate the severity of EE and may have contributed to improvement.393 Figure 1 No Caption available.