S1382 Vonoprazan Dual and Triple Therapy for Helicobacter pylori Eradication

Abstract

Introduction: Eradication rates with standard PPI-based triple therapy (TT) for Helicobacter pylori infection are falling, primarily due to increasing antimicrobial resistance. Here, we present the efficacy and safety results of a Phase 3 trial (PHALCON-HP; NCT04167670) in US and European patients with H pylori, investigating novel TT and dual therapy (DT) regimens containing vonoprazan, an investigational potassium-competitive acid blocker, vs PPI TT. Methods: Patients (N=1046) aged ≥18 years with a positive 13C-urea breath test (13C-UBT) indication of H pylori infection were randomized to 14-day DT with open-label vonoprazan (20 mg two times a day [BID]) and amoxicillin (A; 1 g three times a day [TID]), or double-blind TT with either vonoprazan (20 mg BID) or lansoprazole (L; 30 mg BID), plus A (1 g BID) and clarithromycin (C; 500 mg BID). Eradication was determined by 13C-UBT 4 weeks after treatment. The primary endpoint was the eradication rate in patients without strains resistant to A or C; key secondary endpoints were eradication rates in all patients and in patients with C-resistant strains. The primary endpoint was assessed for non-inferiority (10% margin) of vonoprazan regimens vs LTT; secondary endpoints were assessed for superiority. Safety was also assessed. Results: For the primary endpoint, eradication rates with vonoprazan TT and DT proved non-inferior to LTT in patients with H pylori not resistant to A or C (Table 1): vonoprazan TT 84.7% (P< 0.0001) and vonoprazan DT 78.5% (P=0.0037) vs LTT (78.8%). In all patients, vonoprazan TT and DT were superior to LTT: vonoprazan TT 80.8% (P=0.0001) and vonoprazan DT 77.2% (P=0.0063) vs LTT (68.5%). In patients with C-resistant strains, vonoprazan TT and DT were superior to LTT. Treatment-emergent adverse events (TEAEs) occurred in 32.8% of patients overall; serious TEAEs in 1.3% of patients overall (Table 1). Fifteen patients discontinued treatment due to TEAEs: vonoprazan TT n=8 (2.3%); vonoprazan DT n=3 (0.9%); and LTT n=4 (1.2%). Conclusion: In this large US and European trial, vonoprazan TT and DT were non-inferior to LTT in patients with H pylori strains that were not resistant to C or A. In all patients, and in patients with C-resistant strains, vonoprazan TT and DT were superior to LTT. These data support vonoprazan TT and DT as potential new treatment alternatives to PPI-based TT for H pylori eradication.Table 1.: Key results.