New Drug May Relieve Heartburn in Patients With Refractory Reflux Disease

By Will Boggs MD

March 23, 2020

NEW YORK (Reuters Health) - An investigational bile acid sequestrant called IW-3718 reduces heartburn symptoms in patients with refractory gastroesophageal reflux disease (GERD), according to results from a randomized clinical trial.

"In the era of concern about escalation of acid-suppressive therapy, there may be alternatives, such as IW-3718, to help manage symptoms in those with continued reflux," Dr. Michael F. Vaezi of Vanderbilt University Medical Center, in Nashville, Tennessee, told Reuters Health by email.

GERD affects about 20% of the adult U.S. population, and approximately 30% of GERD patients have symptoms refractory to proton-pump inhibitor (PPI) therapy. Among these patients, nearly two-thirds have duodenogastroesophageal reflux, suggesting that bile acids might be an important target of GERD treatment.

Dr. Vaezi and colleagues at 52 U.S. centers evaluated the safety and efficacy of different doses of IW-3718 as an adjunct therapy to PPIs in 280 patients with GERD who experienced no or only partial relief with PPI treatment.

The percent change from baseline to week 8 in Weekly Heartburn Severity Score (WHSS), the primary efficacy endpoint, was significantly greater with the 1,500 mg dose of IW-3718 (a 58.0% decrease) than with placebo (a 46.0% decrease), the authors report in Gastroenterology.

The change in WHSS did not differ significantly between the IW-3718 500 mg, IW-3718 1,000 mg, and placebo groups.

Weekly Regurgitation Frequency Scores also improved significantly more with IW-3718 1,500 mg (but not with the lower doses), compared with placebo.

Patients treated with IW-3718 1,500 mg experienced numerically greater improvements for all 10 individual symptoms assessed on the Modified Reflux Symptom Questionnaire-Electronic Diary.

Overall, patients treated with IW-3718 had a higher incidence of constipation, nausea, flatulence, upper-respiratory-tract infection, and headache, compared with the placebo group.

"The response of heartburn and regurgitation to medications other than acid-suppressive therapy is a welcome addition to patients with reflux disease, especially those with continued symptoms despite PPI therapy," Dr. Vaezi said.

"I suspect when patients have continued symptoms despite taking their acid-suppressive therapies, then IW-3718 likely will be employed to help manage reflux of gastroduodenal contents and help with residual symptoms," he said.

IW-3718 is being tested in persistent GERD patients in two pivotal phase-3 studies, with early data expected in the second half of 2020.

Ironwood Pharmaceuticals, Inc. funded the study and employed several of the authors.

SOURCE: Gastroenterology, online February 21, 2020.