Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

Abstract

BACKGROUND Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K + /H + -ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan’s suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS Of the 263 randomized, 218 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)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Association Study of Esomeprazole Pharmacokinetics and CYP2C19 Gene Polymorphisms

“…Approximately 70% of the population exhibits a fast metabolizer phenotype, 25% an intermediate metabolizer phenotype, and 5% a slow metabolizer phenotype in the analysis of 2754 White individuals. 6,9,10,14,15 Among Asians, the prevalent CYP2C19 loss-of-function alleles are CYP2C19*2 and CYP2C19*3, chiefly influencing the in vivo metabolism of esomeprazole. 16,17 In the statistical evaluation of 7184 Asians, around 42% of the populace manifests a fast metabolizer phenotype, 45% an intermediate metabolizer phenotype, and 14% a slow metabolizer phenotype.…”

“…In consonance with pertinent literature, extended administration of esomeprazole 40 mg, for a duration exceeding 8 weeks, in patients with esophageal reflux, H. pylori infections, and healthy subjects did not elicit novel safety concerns. 15,23 In synopsis, esomeprazole emerges as a relatively secure PPI, exhibiting favorable tolerability in clinical research settings.…”

“…Within White individuals, the haplotype CYP2C19*17 translating into ultra‐rapid enzymatic activity predominantly impacts in vivo esomeprazole metabolism. Approximately 70% of the population exhibits a fast metabolizer phenotype, 25% an intermediate metabolizer phenotype, and 5% a slow metabolizer phenotype in the analysis of 2754 White individuals 6,9,10,14,15 . Among Asians, the prevalent CYP2C19 loss‐of‐function alleles are CYP2C19*2 and CYP2C19*3 , chiefly influencing the in vivo metabolism of esomeprazole 16,17 .…”

Editorial: deja vu all over again – let the P‐CAB wars begin. Authors' reply

“…In contrast, other P‐CABs such as tegoprazan and fexuprazan have shown comparable increases in serum gastrin levels to esomeprazole, despite their more potent inhibition of gastric acid secretion 5–8 . Tegoprazan increased serum gastrin level to about 200 pg/mL after administration of 200 mg once‐daily for 1 week, while esomeprazole 40 mg increased serum gastrin to about 200 pg/mL.…”

“…4 In contrast, other P-CABs such as tegoprazan and fexuprazan have shown comparable increases in serum gastrin levels to esomeprazole, despite their more potent inhibition of gastric acid secretion. [5][6][7][8] Tegoprazan increased serum gastrin level to about 200 pg/mL after administration of 200 mg once-daily for 1 week, while esomeprazole 40 mg increased serum gastrin to about 200 pg/mL. Similarly, fexuprazan increased serum gastrin level to about 200 and 150 pg/mL after administration of 40 mg once-daily for 1 and 8 weeks, respectively, while esomeprazole 40 mg increased serum gastrin to about 200 and 150 pg/mL, respectively.…”