Tegoprazan curbs nonerosive reflux disease

The novel potassium-competitive acid blocker (P-CAB) tegoprazan has scored high in a phase III trial of Asian patients with nonerosive reflux disease (NERD), showing better efficacy than placebo in terms of complete resolution of major symptoms with a favourable safety profile.

In a cohort of 304 South Korean patients (average age 45 years, 32.6 percent male), complete resolution of both heartburn and regurgitation for the last 7 days of 4 weeks of treatment occurred in 42.5 percent (45 of 106) of patients on tegoprazan 50 mg, 48.9 percent (48 of 99) on tegoprazan 100 mg, and 24.2 percent (24 of 99) on placebo. Both doses were superior to placebo (p=0.0058 and p=0.0004, respectively). [Aliment Pharmacol Ther 2021;doi:10.1111/apt.16477]

Tegoprazan 50 and 100 mg also achieved much higher rates of complete heartburn resolution at week 2 (40.6 percent and 42.4 percent vs 26.3 percent) and week 4 (62.3 percent and 65.7 percent vs 43.4 percent). The proportion of heartburn-free days over the 4-week treatment period was 67.6 percent and 66.5 percent, respectively, relative to 56.7 percent with placebo (p=0.0103 and p=0.0210). These results were consistent in the subgroup analysis of patients who reported moderate-to-severe heartburn during the screening period.

“The responses for complete resolution rates of heartburn observed in this study were comparable with those previously obtained with proton pump inhibitors (PPIs) in patients with NERD,” the investigators pointed out. [J Gastroenterol 2008;43:670-678; Aliment Pharmacol Ther 2011;33:213-224]

In terms of safety, the incidence of treatment-emergent adverse events (TEAEs) were similar across the three treatment arms—19.4 percent with tegoprazan 50 mg, 22.2 percent with 100 mg, and 20.6 percent with placebo. Most TEAEs were mild in severity, with nausea, headache, and nasopharyngitis being the most common. There were no reports of severe or unexpected serious TEAEs and death.

NERD is characterized by the presence of typical gastroesophageal reflux disease (GERD) symptoms without oesophageal erosion at upper endoscopy, and this can have a negative influence on the quality of life of patients, according to the investigators. [Aliment Pharmacol Ther 2005;22:41-47]

“PPIs are currently … the most effective treatment for GERD, but reflux symptoms are not completely controlled in a significant number of patients with NERD,” they said, adding that the responses to PPI therapy have been shown to be higher in patients with erosive vs nonerosive reflux disease. This suggests that these two disorders might have different underlying pathogeneses. [Aliment Pharmacol Ther 2007;26:69-77; J Clin Gastroenterol 2007;41:131-137]

As a P-CAB, tegoprazan inhibits the proton pump through a competitive interaction with the potassium site of the enzyme without acid activation, the investigators explained. “P-CAB blocks the active and the inactive forms of the proton pump. Thus, P-CAB inhibits the gastric acid secretion rapidly and for longer time, which could also improve the clinical outcomes, such as heartburn and regurgitation, in patients with NERD.” [J Neurogastroenterol Motil 2019;25:6-14; Clin Pharmacokinet 2016;55:409-418; Pharmacol Ther 2016;168:12-22]

Despite the limitations of the trial, including the lack of an active comparator and information on disposition of patients infected with Helicobacter pylori, the findings indicate that tegoprazan may provide an effective therapeutic option for the treatment of NERD.

In South Korea, tegoprazan is approved for the treatment of erosive and nonerosive reflux diseases, gastric ulcer, and eradication of Helicobacter pylori. It is the first P-CAB clinically available for patients with NERD. [Intern Med 2018;57:2443-2450; Aliment Pharmacol Ther 2019;49:864-872]