GSK, Spero Therapeutics resubmits NDA for tebipenem HBr as oral option for complicated urinary tract infections

GSK and Spero Therapeutics have resubmitted a New Drug Application (NDA) to the FDA for tebipenem HBr, an investigational oral carbapenem antibiotic for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, according to an announcement from Spero Therapeutics, Inc. ¹

Tebipenem HBr is being evaluated as a potential oral treatment option for cUTIs, a category of infections that often require hospitalization and intravenous antibiotic therapy, particularly when caused by multidrug-resistant pathogens. Carbapenem antibiotics are commonly used in severe or resistant infections, but currently require intravenous administration.

Phase 3 PIVOT-PO trial results

The NDA resubmission is supported by data from the global, randomized, double-blind Phase 3 PIVOT-PO trial (ClinicalTrials.gov identifier: NCT06059846), which compared oral tebipenem HBr with intravenous imipenem-cilastatin in hospitalized adults with cUTIs, including pyelonephritis. The study was stopped early for efficacy in May 2025 following a planned interim analysis, and results were presented at IDWeek 2025.²

The trial met its primary endpoint, demonstrating noninferiority of oral tebipenem HBr compared with intravenous imipenem-cilastatin based on overall response at the test-of-cure visit. Overall response was defined as a composite of clinical cure and microbiological eradication. Tebipenem HBr achieved an overall success rate of 58.5% (261 of 446 patients), compared with 60.2% (291 of 483 patients) for imipenem-cilastatin, with an adjusted treatment difference of 1.3% (95% CI, −7.5% to 4.8%)

Secondary endpoints also supported comparable efficacy between treatment groups. Clinical cure rates at the test-of-cure visit were 93.5% in the tebipenem HBr group and 95.2% in the imipenem-cilastatin group. Microbiological response rates were 60.3% and 61.3%, respectively. Clinical and microbiological response rates among patients with infections caused by antimicrobial-resistant Enterobacterales were consistent with those observed in the overall study population.

Safety and tolerability

The safety profile of tebipenem HBr was generally similar to that of other carbapenem antibiotics. The most frequently reported adverse events among patients receiving tebipenem HBr were diarrhea and headache, each occurring in at least 3% of patients. These events were described as mild or moderate and nonserious.

Potential clinical implications

Commenting on the trial results, Tony Wood, chief scientific officer at GSK, said, “These ground-breaking data show for the first time that cUTIs, including pyelonephritis, can be treated with an oral carbapenem antibiotic as effectively as with an intravenous one.” He added that tebipenem HBr “could be taken at home,” highlighting the potential for greater treatment flexibility.

Esther Rajavelu, CEO of Spero Therapeutics, stated, “These data presented at IDWeek represent the culmination of years of dedicated work by our team in close collaboration with GSK,” and noted that the companies are focused on advancing tebipenem HBr toward regulatory approval.

If approved, tebipenem HBr could become the first oral carbapenem antibiotic available in the United States for patients with cUTIs. An effective oral option may allow selected patients to avoid prolonged hospitalization or outpatient parenteral antibiotic therapy, depending on clinical status and pathogen susceptibility.

GSK will continue to work with US regulatory authorities as part of the NDA review process. A timeline for FDA action on the resubmission was not disclosed.

References

1. Spero Therapeutics. Spero Announces NDA Resubmission of Tebipenem HBr by GSK to the FDA for the Treatment of Complicated Urinary Tract Infections, Including Pyelonephritis. Globe Newswire. 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. PIVOT-PO Phase 3 Data Show Tebipenem HBr's Potential as the First Oral Carbapenem Antibiotic for Patients with Complicated Urinary Tract Infections (cUTIs). Press release. October 21 ,2025. Accessed December 19, 2025. https://www.gsk.com/en-gb/media/press-releases/positive-pivot-po-phase-iii-data-show-tebipenem-hbr-s-potential-as-the-first-oral-carbapenem-antibiotic-for-patients-with-complicated-urinary-tract-infections-cutis/