Published online Nov 28, 2022. doi: 10.3748/wjg.v28.i44.6294
Peer-review started: September 4, 2022
First decision: October 4, 2022
Revised: October 17, 2022
Accepted: November 9, 2022
Article in press: November 9, 2022
Published online: November 28, 2022
Processing time: 81 Days and 14.1 Hours
Currently, a mainstay therapy of erosive esophagitis (EE) is proton pump inhibitors (PPIs), which have disadvantages like their delayed absorption and variable efficacy due to differences in drug metabolism A novel potassium-competitive acid blocker, fexuprazan, suppresses the K+/H+-ATPase enzyme reversibly and competetively in proton pumps within gastric parietal cells.
A previous study of fexuprazan on healthy individuals demonstrated the effect of its acid suppression and tolerability, by showing that gastric pH > 4 was reached within 2 h and maintained for 24 h in a dose-dependent manner. However, the efficacy and safety of fexuprazan in EE have not been compared to esomeprazole, one of the most widely used PPIs in gastro-esophageal reflux disease (GERD) including EE.
The aim of this phase III, double-blind, randomized, active-controlled, multi-center study was to compare the efficacy and safety between fexuprazan and esomeprazole in patients with EE.
Adult patients who have EE confirmed by endoscopy were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks in South Korea between December 2018 and August 2019. The primary endpoint was healing rates confirmed by endoscopy at week 8. The secondary endpoints included the proportion of patients with healed EE at week 4, symptom response, and GERD-related quality of life assessed from the evaluation through the symptom diary, reflux disease questionnaire (RDQ) and GERD-health related quality life (GERD-HRQL) questionnares. We also compared safety profiles and serum gastrin levels between the groups.
This study shows that fexuprazan 40 mg once daily is non-inferior to esomeprazole 40 mg once daily in healing rates of at weeks 4 and 8 and in symptom improvement of heartburn and acid regurgitation and RDQ and GERD-HRQL. In 218 participants who completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111), fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)], and at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Also, serum gastrin levels at weeks 4 and 8 and drug-related side effects were not significantly different between the groups.
This study results indicate that fexuprazan 40 mg once daily can be an alternative of esomeprazole 40 mg once daily for patients with erosive esophagitis in terms of efficacy and safety.
Further research on fexuprazan should be directed to evaluate the long-term efficacy and safety of fexuprazan in various acid-related gastrointestinal diseases including NERD, PPI-refractory GERD, H. pylori infection, peptic ulcer diseases, and so on.