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Novel bile acid sequestrant relieves symptoms of GERD
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SAN DIEGO — A novel bile acid sequestrant helped improve heartburn and regurgitation in patients with persistent GERD who continued receiving proton pump inhibitors, according to study results presented at Digestive Disease Week.
Michael F. Vaezi , MD, PhD, of Vanderbilt University Medical Center, said the drug — IW-3718 (Ironwood Pharmaceuticals) — could be a helpful adjunct to PPI therapy.
“Proton pump inhibitors are front-line therapy for [GERD] but not completely effective in some of our patients,” he said in his presentation. “Bile acids, we’ve done work in the past, as well as others, that has shown that it does play a role in the pathogenesis of reflux, such as esophagitis and possibly Barrett’s. ... Could it also be playing a role in persistent reflux?”
Vaezi and colleagues previously found that the drug was effective in treating GERD, but in this study, they explored its impact on specific symptoms.
Researchers included 280 patients with GERD who had to have heartburn or regurgitation for at least 4 days per week for 8 weeks despite ongoing PPI use. After a two-week pretreatment phase, they randomly assigned patients to receive either 500 mg, 1,000 mg or 1,500 mg of IW-3718 or placebo twice daily for 8 weeks in addition to PPIs once a day.
Patients reported the severity and frequency of 10 symptoms associated with GERD at baseline, including heartburn, regurgitation, pain and burping. The main outcome for the study was change in scores at week 8.
Vaezi and colleagues observed that there was a dose-response relationship, with patients who received 1,500 mg of the drug experiencing improvements for all symptoms in both severity and frequency compared with placebo (P .05), except for burping frequency.
“The novel gastric-retentive bile acid sequestrant IW-3718 was efficacious in reducing a spectrum of symptoms in patients with persistent GERD, whether it be symptoms that were assessed by severity or by frequency,” Vaezi concluded, adding that phase 3 studies are in the works. – by Alex Young
Reference:
Vaezi MF, et al. Abstract 12; Presented at; Digestive Disease Week; May 18-21, 2019; San Diego.
Disclosures: Vaezi reports serving on the medical advisory board for Ironwood Pharmaceuticals. Please see the full meeting disclosure index for all other authors’ relevant financial disclosures.
Perspective
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Kenneth DeVault, MD, FACG
Somewhere between 20% and 40% of patients with GERD will experience symptoms that are at least partially refractory to therapy with proton pump inhibitors. This is not surprising as those agents suppress acid but actually do not prevent the reflux of all acid and non-acidic materials from the stomach into the esophagus. Agents to address this challenging group of patients have concentrated on providing more complete acid suppression or improving motility of the lower esophagus but positive results have been lacking. The concept of bile reflux in refractory patients has been extensively debated with some believing it to be a cause of symptoms and even malignant transformation while others discount it as a major factor. This study certainly challenges those who have been discounting the role of bile in refractory reflux symptoms.
This study is a phase 2 trial of a newly formulated bile acid binder that is designed to stay in the stomach for a protracted period. The patient population was patients with well-established GERD who had symptoms refractory to once daily PPI therapy. They found that this agent produced an improvement in all GERD symptoms except for burping, compared with placebo.
Assuming this agent is approved (currently in phase 3 trials), these data support using it in refractory patients. It is important to know that these patients had well established, probably severe GERD (esophagitis or positive pH study while on once daily PPI) and had heartburn or regurgitation as their primary refractory symptom. One would assume that patients with less well-proved GERD and those with atypical symptoms would not fare as well.
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