Tegoprazan may be a clinically meaningful alternative to PPIs for maintaining healing in erosive esophagitis and providing heartburn relief.Results from the phase III TRIUMpH-EE study demonstrate the superiority of the novel potassium-competitive acid blocker (P-CAB) tegoprazan over the proton pump inhibitor (PPI) lansoprazole in providing faster healing of erosive esophagitis (EE) and heartburn relief.
Healing phase: 8 weeks
In the healing phase, 1,245 patients with endoscopically confirmed EE (mean age 53 years, 52 percent women, 37 percent Los Angeles [LA] C/D) were randomized 1:1 to tegoprazan 100 mg or lansoprazole 30 mg QD for up to 8 weeks. [DDW 2026, abstract 619]
Tegoprazan met the primary endpoint, demonstrating noninferiority and superiority to lansoprazole for complete endoscopic healing in all patients (LA Grade A–D) by week 8 in the modified intention-to-treat population (84.6 percent vs 78 percent; p for noninferiority<0.0001 and p for superiority=0.0083).
All hierarchical secondary endpoints achieved statistical significance, including the superiority of tegoprazan for complete endoscopic healing in all patients at week 2 (76.4 percent vs 67 percent; p<0.0001) and in patients with severe disease (LA Grade C/D) at weeks 2 (74.1 percent vs 54.5 percent; p<0.0001) and 8 (83.2 percent vs 68 percent; p=0.0002).
Tegoprazan was noninferior to lansoprazole for 24-hr heartburn-free days (HBFD) in all patients (54.3 percent vs 51.9 percent; p<0.0001) and demonstrated superior heartburn control in the severe subgroup (60.1 percent vs 53.6 percent; p=0.0289) at week 8.
Both tegoprazan and lansoprazole groups showed no significant differences in the rates of treatment-emergent adverse events (TEAEs; 30.8 percent vs 31.2 percent), serious TEAEs (1.8 percent vs 0.6 percent), drug-related TEAEs (8.2 percent vs 7.6 percent), TEAEs leading to discontinuation (3.2 percent vs 1.4 percent), and AEs of special interest (1.8 percent vs 3.1 percent).
Unsatisfactory PPI Tx
Approximately one-third of patients with gastroesophageal reflux disease (GERD) are ultimately diagnosed with EE. [Cureus 2023;15:e47420] Up to half of patients on PPI fail to achieve symptom relief, leading to dissatisfaction with PPI therapy. [Dig Dis Sci 2010;55:3415-3422; Foregut 2024;1:32-39]
“GERD is highly prevalent and remains associated with significant unmet needs. Many patients continue to experience symptoms despite PPI therapy,” said Dr Felice Schnoll Sussman from the Weill Cornell Medical Center, New York, New York, US, at DDW 2026.
P-CABs are potent acid suppressants that provide rapid and sustained acid control with comparable or superior efficacy to PPIs in EE. Some of the major differences between PPIs and P-CABs are that PPIs require acid activation, and proton pumps are inhibited only in their active states. Conversely, P-CABs require no acid activation, and there are proton pump binding sites in both active and resting states, noted Sussman.
“PPI efficacy is dependent upon timing relative to meals, which can truly affect compliance. With P-CABs, acid control is independent of meal intake,” she said.
“Tegoprazan offers multiple potential mechanistic advantages over PPIs … Its self-regulating binding mechanism of action enables rapid onset—achieving pH >4 within 45 mins, steady state within one day, stable pH control without excessive spikes, and maintenance of gastrin levels within normal range,” she explained.
“Tegoprazan 100 mg is the first and only P-CAB to demonstrate superior healing of EE compared with a PPI across all severity grades, with three out of four patients healed by week 2,” said Sussman.
Sussman added that tegoprazan offers clinically important advantages over lansoprazole in healing and heartburn relief, particularly in LA Grade C/D EE.
“Given the rapid healing, superior symptom relief, and favourable safety profile, tegoprazan 100 mg may address substantial unmet clinical needs compared with PPIs across all grades of EE,” Sussman concluded.
Maintenance phase: 24 weeks
TRIUMpH-EE participants with endoscopically confirmed healing at week 2 or 8 entered the maintenance phase (n=944) and were randomized 1:1:1 to tegoprazan 50 or 100 mg or lansoprazole 15 mg. [DDW 2026, abstract 962]
Tegoprazan 50 mg demonstrated noninferiority and superiority to lansoprazole for the maintenance of endoscopic healing at week 24 in all patients (61.4 percent vs 50.6 percent; p for noninferiority=0.008 and p for superiority=0.0145). Greater efficacy was observed with the 100-mg dose (69.4 percent vs 50.6 percent; p for noninferiority=0.0002 and p for superiority<0.0001).
Tegoprazan 100 mg was also superior to lansoprazole in the severe subgroup in maintaining endoscopic healing (76.4 percent vs 44.3 percent; p<0.0001) and achieving 24-hr HBFD (84.2 percent vs 70.4 percent; p=0.0018) at week 24.
Moreover, both tegoprazan doses were noninferior to lansoprazole for 24-hr HBFD over 24 weeks in all patients (69.9 percent [50 mg] and 72.9 percent [100 mg] vs 69.4 percent; p<0.0001 for both comparisons).
The safety profile at week 24 was consistent with that observed at week 8. “There were no [new] safety signals with either tegoprazan dose. Of note, there were no hepatotoxicity signals with tegoprazan, which were issues when P-CABs were initially introduced,” noted Dr C Prakash Gyawali from the Washington University School of Medicine, St Louis, Missouri, US, at DDW 2026.
High therapeutic gains
“Tegoprazan demonstrated superior maintenance of healing and sustained heartburn control compared with lansoprazole across all grades of EE, with the 100-mg dose being the most effective dose in all endpoints,” Gyawali said.
There were additional therapeutic gains for LA Grade C/D patients of approximately 32 percent in the maintenance of healing and 14 percent in heartburn control over lansoprazole with tegoprazan 100 mg, he continued.
“The efficacy and safety results support tegoprazan as a clinically meaningful alternative to PPIs in the maintenance of EE healing, especially in severe grades,” Gyawali concluded.