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, controlled trial conducted across 40 hospitals in China demonstrated that rifasutenizol-based triple therapy is superior to the current standard of care, bismuth-containing quadruple therapy (BQT).
The study 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 BQT control group (92.0% vs. 87.9%, difference 4.1%, non-inferiority test p<0.0001, superiority test p=0.0338). Similar results were observed in the per protocol (PP) population (93.7% vs. 90.3%, difference 3.4%, non-inferiority test p<0.0001, superiority test p=0.0563).
Efficacy Against Antibiotic-Resistant Strains
Notably, the rifasutenizol regimen also demonstrated higher eradication rates in patients infected with H. pylori strains resistant to commonly used antibiotics (90.9% vs. 87.2%, difference 3.7%, non-inferiority test p<0.0001). The resistance rates to clarithromycin, metronidazole, and levofloxacin were 41%, 68%, and 35%, respectively, consistent with recent reports indicating a significant challenge with antibiotic resistance in China. All clinical isolates in the study were susceptible to rifasutenizol.
Improved Safety and Tolerability
The rifasutenizol regimen exhibited a better 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.
Potential Impact on Gastric Cancer Prevention
H. pylori infection is a major risk factor for gastric cancer, particularly in populations with high gastric cancer incidence. Rifasutenizol, with its novel multi-targeting mechanism of action, has the potential to become the first new drug developed specifically for H. pylori infection in over 30 years. According to TenNor, the rifasutenizol regimen does not require drug sensitivity testing and can be seamlessly integrated with UBT testing, making it a valuable tool in large-scale test-and-treat strategies for gastric cancer prevention.
