GSK has refiled a new drug application (NDA) to the FDA for tebipenem pivoxil hydrobromide (HBr). This investigational oral carbapenem antibiotic is aimed at treating complicated urinary tract infections (cUTI), particularly pyelonephritis. The initial NDA was submitted in 2022. However, the FDA required additional data to move forward with approval.
Key Details of the Application
GSK’s current NDA is bolstered by positive outcomes from the phase 3 PIVOT-PO trial (NCT06059846). This trial met its primary endpoint, demonstrating that tebipenem HBr was noninferior to imipenem-cilastatin in terms of overall response rate at the test-of-cure (TOC) visit.
- Trial Enrollment: 1,690 patients with cUTI, including acute pyelonephritis.
- Treatment Regimen: 600 mg tebipenem HBr orally every 6 hours or 500 mg intravenous imipenem-cilastatin every 6 hours.
- Trial Duration: 7 to 10 days.
Results of the PIVOT-PO Trial
The study’s primary endpoint involved evaluating the overall response rate, defined as the combination of clinical cure and microbiological eradication. Key findings included:
- Overall Success Rate: 58.5% for tebipenem HBr vs. 60.2% for imipenem-cilastatin (adjusted difference: 1.3%).
- Clinical Cure Rate: 93.5% in the tebipenem HBr group versus 95.2% in the imipenem-cilastatin group (adjusted difference: 1.6%).
- Microbiological Response Rate: 60.3% for tebipenem HBr compared to 61.3% for imipenem-cilastatin (adjusted difference: 0.8%).
These success rates were consistent even among patients with infections caused by antimicrobial-resistant Enterobacterales. The trial was concluded early for efficacy following an interim data analysis conducted in May 2025.
Safety Profile and Adverse Events
The safety profile of tebipenem HBr aligns with that of other carbapenem antibiotics. The most frequently reported adverse events were diarrhea and headache, which were categorized as mild to moderate and non-serious.
The results from the PIVOT-PO trial were showcased as a late-breaking abstract at IDWeek 2025, highlighting the significance of this research in the quest for effective treatments for cUTI.
