TenNor Therapeutics announced positive topline results from its Phase III clinical trial evaluating rifasutenizol (TNP-2198) for the treatment of Helicobacter pylori (H. pylori) infection. The multi-center, randomized, double-blind study, conducted across 40 hospitals in China, demonstrated that rifasutenizol-based triple therapy is more effective and safer than the current standard of care, bismuth-containing quadruple therapy (BQT).
The trial enrolled 700 treatment-naive patients with H. pylori infection, confirmed by a positive carbon-13 urea breath test (C-13 UBT) and histological examination. Participants were randomized 1:1 to receive either rifasutenizol triple therapy (rifasutenizol 400 mg, amoxicillin 1 g, and rabeprazole 20 mg) or BQT (bismuth potassium citrate 240 mg, clarithromycin 500 mg, amoxicillin 1 g, and rabeprazole 20 mg), administered twice daily for 14 days. The primary efficacy endpoint was the C-13 UBT result 4 to 6 weeks post-treatment.
Superior Eradication Rates with Rifasutenizol
The rifasutenizol triple therapy achieved an eradication rate exceeding 90% in the modified intention-to-treat (mITT) population, significantly higher than the 87.9% observed in the BQT group (difference 4.1%, superiority test p=0.0338, non-inferiority test p<0.0001). In the per-protocol (PP) population, rifasutenizol also showed a higher eradication rate (93.7% vs. 90.3% for BQT), although the superiority test did not reach statistical significance (p=0.0563, non-inferiority test p<0.0001).
Efficacy Against Antibiotic-Resistant Strains
Notably, the rifasutenizol regimen demonstrated robust efficacy even in patients infected with H. pylori strains resistant to commonly used antibiotics. In this subgroup, rifasutenizol triple therapy achieved a 90.9% eradication rate compared to 87.2% with BQT (difference 3.7%, non-inferiority test p<0.0001). The study reported resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin at 41%, 68%, 35%, and 8%, respectively, consistent with recent data indicating a significant challenge posed by antibiotic resistance in H. pylori treatment in China. Importantly, all clinical isolates from the study were susceptible to rifasutenizol.
Improved Safety and Tolerability
Rifasutenizol also exhibited a more favorable safety and tolerability profile compared to BQT. The incidence of treatment-emergent adverse events (TEAEs), investigational drug-related TEAEs, and grade 3 or higher TEAEs were all lower in the rifasutenizol arm. Most TEAEs were grade 1, and no investigational drug-related serious adverse events (SAEs) were reported.
Rifasutenizol, a novel multi-targeting drug candidate, has the potential to become the first new drug specifically developed for H. pylori infection in over 30 years. Its unique mechanism of action and demonstrated efficacy against resistant strains could make it a crucial component of large-scale test-and-treat strategies aimed at preventing gastric cancer, particularly in high-risk populations. The rifasutenizol regimen's independence from drug sensitivity testing further streamlines its integration with UBT-based diagnostic approaches.
