Bile acid sequestrant improves effects of PPI in persistent GERD

WASHINGTON — A bile acid sequestrant improved heartburn and regurgitation when paired with a proton pump inhibitor in patients with persistent GERD, according to the results of a phase 2b trial presented at Digestive Disease Week.

These data also suggested that IW-3718 (Ironwood Pharmaceuticals) — a novel formulation of the bile acid sequestrant colesevelam that is retained in the stomach to intercept bile before it reaches the esophagus — also improved symptoms in patients with erosive esophagitis.

“These data are encouraging for physicians who continue to see their patients with GERD struggle with frequent and bothersome symptoms despite taking PPIs,” study investigator and DDW presenter Michael Frederick Vaezi, MD, PhD, professor of medicine in the division of gastroenterology, hepatology and nutrition, and director of the Center for Swallowing and Esophageal Disorders at Vanderbilt University Medical Center, said in a press release. “In addition to holding promise for patients with persistent GERD, these results show that IW-3718 also has potential in patients who also have erosive esophagitis despite PPI therapy — a serious condition that can cause severe damage and injury to the esophagus.”

To evaluate the efficacy of IW-3718 as an add-on therapy for patients with persistent GERD on a standard dose of PPIs, Vaezi and colleagues randomized 282 patients who had GERD with erosive esophagitis (51.8%) and/or abnormal pH, and persistent heartburn or regurgitation despite once daily PPI therapy. They randomly assigned patients to receive placebo or one of three doses of IW-3718 for 8 weeks in addition to their PPI.

Patients showed a dose-response with the study drug, with the clearest difference vs. placebo seen with the highest dose of 1,500 mg. At week 8, heartburn severity scores significantly improved with 1,500 mg of the study drug vs. placebo (P = .04), as did regurgitation scores (P = .01). Improvement in heartburn severity was seen as early as week 2, especially in patients with erosive esophagitis.

Overall, 52.9% of patients in the 1,500-mg arm reported clinically meaningful improvements in heartburn symptoms and 46.3% reported improvements in regurgitation compared with 37.1% and 34.3% in the placebo group. Again, patients with erosive esophagitis showed even greater improvements.

Six patients experienced serious adverse events that were deemed unrelated to the study drug, and 10 patients withdrew from the study due to adverse events, the most common of which was constipation (7.4% to 8.1% with study drug vs. 7.1% with placebo).

“The data presented at this meeting provide strong validation of our approach of targeting bile acid reflux in addition to suppressing stomach acid with PPIs and reinforce our belief that IW-3718 may bring a new approach to treating these patients for whom available options don’t work,” Mark Currie, PhD, senior vice president, chief scientific officer, and president of research and development at Ironwood, said in the press release. “We are excited by the results and are actively working to start phase 3 trials shortly.” – by Adam Leitenberger

Reference:

Vaezi MF, et al. Abstract 875. Presented at: Digestive Disease Week; June 2-5, 2018; Washington, D.C.

Disclosures: Vaezi reports he has served on the medical advisory board for Ironwood and reports a financial relationship with Diversatek. Currie is employed by Ironwood. Please see the DDW faculty disclosure index for a list of all other authors’ relevant financial disclosures.