FDA approval sought for tebipenem HBr for complicated urinary tract infections

GSK has resubmitted a new drug application (NDA) to the FDA seeking approval of tebipenem pivoxil hydrobromide (HBr), an investigational oral carbapenem antibiotic for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis.¹

The application was initially submitted in 2022, but the agency determined that additional data were needed for approval.² The current application is supported by results from the phase 3 PIVOT-PO trial (NCT06059846), which met its primary end point by showing that tebipenem HBr was noninferior to imipenem-cilastatin in regard to the overall response rate (composite of clinical cure plus microbiological eradication) at the test-of-cure (TOC) visit in hospitalized adult patients with cUTI.

The trial was stopped early for efficacy following an interim analysis of the data in May 2025. Results from the study were presented as a late-breaking abstract at IDWeek 2025.³

In total, the global, double-blind trial had enrolled 1690 patients with cUTI, including acute pyelonephritis. Patients in the trial were randomly assigned 1:1 to receive 600 mg tebipenem pivoxil orally every 6 hours or 500 mg intravenous imipenem-cilastatin every 6 hours for a total of 7 to 10 days. The trial’s primary end point was overall response rate (consisting of a composite score of clinical cure plus microbiological eradication) at the test-of-cure (TOC) visit (about 17 days from first dose administration of study drug) in patients with qualifying pathogens susceptible to imipenem.

Data showed an overall success rate of 58.5% among those who received tebipenem HBr compared with an overall success rate of 60.2% among those who received imipenem-cilastatin (adjusted treatment difference: 1.3%; 95% CI, 7.5% to 4.8%).

Further, clinical cure at the TOC visit was achieved in 93.5% of patients in the tebipenem HBr cohort vs 95.2% in the imipenem-cilastatin cohort (adjusted treatment difference, 1.6%; 95% CI, 4.7% to 1.4%). The rates of microbiological response at the TOC visit were 60.3% in the tebipenem HBr arm compared to 61.3% in the imipenem-cilastatin arm (adjusted treatment difference, 0.8%; 95% CI, 6.9% to 5.3%).

In patients with infections caused by antimicrobial-resistant Enterobacterales, clinical and microbiological response rates were consistent with what was observed in the overall population.

The safety profile for tebipenem HBr was also consistent with that of other carbapenem antibiotics. The most common adverse events in the trial were diarrhea and headache, all of which were mild to moderate and non-serious.

REFERENCES

1. Spero announces NDA resubmission of tebipenem HBr by GSK to the FDA for the treatment of complicated urinary tract infections, including pyelonephritis. News release. Spero Therapeutics. December 19, 2025. Accessed December 19, 2025. https://www.globenewswire.com/news-release/2025/12/19/3208446/0/en/Spero-Announces-NDA-Resubmission-of-Tebipenem-HBr-by-GSK-to-the-FDA-for-the-Treatment-of-Complicated-Urinary-Tract-Infections-Including-Pyelonephritis.html

2. Spero Therapeutics receives complete response letter from U.S. Food and Drug Administration for tebipenem HBr new drug application. Published online June 27, 2022. Accessed June 28 2022. https://www.globenewswire.com/news-release/2022/06/27/2469890/0/en/Spero-Therapeutics-Receives-Complete-Response-Letter-from-U-S-Food-and-Drug-Administration-for-Tebipenem-HBr-New-Drug-Application.html

3. PIVOT-PO phase 3 data show tebipenem HBr's potential as the first oral carbapenem antibiotic for patients with complicated urinary tract infections (cUTIs). News release. Spero Therapeutics. October 21, 2025. Accessed December 19, 2025. https://s3.amazonaws.com/b2icontent.irpass.cc/2748/rl158673.pdf