Phase 3 trial of tebipenem HBr for cUTI stopped early for efficacy

GSK and Spero Therapeutics announced that the pivotal phase 3 PIVOT-PO trial (NCT06059846) of tebipenem pivoxil hydrobromide (HBr) for complicated urinary tract infection (cUTI) has been stopped early following an interim analysis of the data showing that the trial met its primary end point.¹

Tebipenem HBr was previously granted qualified infectious disease product and fast track designations from the FDA.

The decision was made based on a recommendation from the Independent Data Monitoring Committee (IDMC), which conducted an analysis of the first 1690 patients in the study. The IDMC concluded that the trial met its primary end point by showing that tebipenem HBr was noninferior to imipenem-cilastatin on overall response rate (composite of clinical cure plus microbiological eradication) at the test-of-cure (TOC) visit in hospitalized adult patients with cUTI.

There were no new safety concerns beyond the known safety profile of tebipenem, the IDMC also reported. The 2 most common adverse events in the study were diarrhea and headache.

According to GSK, these data are intended to support a new drug application to the FDA for approval of tebipenem HBr, expected to be submitted in the second half of 2025. If approved, tebipenem HBr would become the first oral carbapenem antibiotic cleared for patients with cUTI. The results will also be shared at upcoming medical meetings.

“We’re proud of today’s positive result for patients diagnosed with cUTI, including pyelonephritis, where oral treatments are much needed,” said Esther Rajavelu, CEO of Spero Therapeutics, in the news release.¹ “We look forward to working with GSK on next steps for tebipenem HBr, and would like to thank the patients, investigators, and other clinical staff who have participated in [the] PIVOT-PO trial to reach this advanced stage.”

GSK entered into an exclusive license agreement with Spero Therapeutics in September 2022 for support in the development and commercialization of tebipenem HBr in all markets aside from Asian territories.

About PIVOT-PO

Overall, the global, double-blind PIVOT-PO trial included 1690 hospitalized patients with cUTI, including acute pyelonephritis, to compare the safety and efficacy of tebipenem HBr vs intravenous (IV) imipenem. To be eligible for enrollment, patients needed to have a diagnosis of cUTI or acute pyelonephritis, an adequate urine specimen with evidence of pyuria, and an expectation per the investigator that the patient would survive with effective antimicrobial therapy and appropriate care for the duration of the study.²

Those enrolled in the trial were randomly assigned 1:1 to receive 600 mg of tebipenem HBr orally every 6 hours or 500 mg IV imipenem-cilastatin every 6 hours for a total of 7 to 10 days. The primary end point for the trial was overall response rate (consisting of a composite score of clinical cure plus microbiological eradication) at the TOC visit.

In 2022, GSK’s EAGLE 2 and EAGLE 3 trials for gepotidacin were also halted early for efficacy. Gepotidacin (Blujepa) was approved by the FDA in March 2025 for the treatment of female adults (40 kg and over) and adolescents (aged 12 years and older; 40 kg and over) with uncomplicated UTIs caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.³

Tebipenem HBr was previously granted qualified infectious disease product and fast track designations from the FDA for cUTI and acute pyelonephritis.

REFERENCES

1. PIVOT-PO phase III study for tebipenem HBr stopped early for efficacy following review by Independent Data Monitoring Committee. News release. GSK. May 28, 2025. Accessed May 28, 2025. https://www.gsk.com/en-gb/media/press-releases/pivot-po-phase-iii-study-for-tebipenem-hbr-stopped-early-for-efficacy-following-review-by-independent-data-monitoring-committee/

2. A study of oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) compared to intravenous imipenem-cilastatin in participants with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) (PIVOT-PO). ClinicalTrials.gov. Last updated May 23, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT06059846

3. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older. News release. GSK. March 25, 2025. Accessed May 28, 2025. https://www.gsk.com/en-gb/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections/