Today, Spero Therapeutics and GSK announced their PIVOT-PO phase 3 study was stopped early for efficacy following review by an independent data monitoring committee (IDMC) that completed a pre-specified interim analysis of participants enrolled in the trial.
The trial met the primary endpoint of non-inferiority of oral tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized adult patients with cUTI, including pyelonephritis, on overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit.
In terms of safety, the IDMC review did not identify any new concerns beyond what has been reported in other studies with the antibiotic, which included diarrhea and headache as the 2 most reported adverse events.
“Achieving the primary endpoint in the PIVOT-PO trial marks a significant milestone for tebipenem HBr,” Spero CEO Esther Rajavelu said in a statement. “If approved, we believe tebipenem HBr is well positioned to change the treatment landscape for patients diagnosed with cUTI, including pyelonephritis.”
Tebipenem pivoxil hydrobromide (HBr) is a late-stage development asset developed in collaboration with GSK.
Study Specifics
PIVOT-PO is a global, randomized, double-blind, pivotal phase 3 clinical trial of oral tebipenem HBr versus IV imipenem cilastatin, in hospitalized adult patients with cUTI including pyelonephritis. Patients were randomized 1:1 to receive tebipenem HBr (600 mg) orally every six hours, or imipenem cilastatin (500 mg) IV every six hours, for a total of seven to ten days. The primary efficacy endpoint is overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit.
The primary analysis for the trial is an assessment of non-inferiority (NI) in the microbiological intention-to-treat population, based on a 10% NI margin. The trial enrolled a total of 1690 patients, with randomization stratified by age, baseline diagnosis (cUTI including pyelonephritis), and the presence or absence of urinary tract instrumentation.
What You Need to Know
The PIVOT-PO trial was stopped early due to positive efficacy results based on a pre-specified interim analysis by an independent data monitoring committee. This suggests oral tebipenem HBr is as effective as IV imipenem-cilastatin in treating complicated urinary tract infections (cUTIs), including pyelonephritis, which could pave the way for more accessible outpatient treatment options.
Tebipenem HBr met its primary endpoint of non-inferiority in terms of overall response (clinical cure plus microbiological eradication), indicating it could be a viable oral alternative to current IV treatments for cUTIs. This is particularly important for reducing hospital stays and healthcare costs.
GSK plans to submit the data to the FDA in the second half of 2025, aiming for regulatory approval. If approved, tebipenem HBr could become the first oral carbapenem available for drug-resistant cUTIs, addressing a major unmet need in infectious disease treatment.
cUTI Burden
An estimated 2.9 million cases of cUTIs are treated annually in the US alone.1 And cUTIs account for over 626,000 hospital admissions annually in the US representing approximately 1.8% of all hospitalizations. And 80% of these cases are non-catheter-related. 3“Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock,” GSK Chief Scientific Officer Tony Wood said in a statement. “Currently many need hospital-based intravenous treatment due to limited oral options for drug-resistant infections, contributing to over $6 billion per year in US healthcare costs.”1
Next Steps
GSK plans to work with US regulatory authorities to include the data as part of a filing for FDA approval in the second half of 2025. “We look forward to working with GSK on next steps for this program,” Rajavelu said.
References
1.Spero Therapeutics and GSK Announce PIVOT-PO Phase 3 Study for Tebipenem HBr Stopped Early for Efficacy Following Review by Independent Data Monitoring Committee. Spero press release. May 28, 2025. Accessed May 28, 2025.
https://www.globenewswire.com/news-release/2025/05/28/3089331/0/en/Spero-Therapeutics-and-GSK-Announce-PIVOT-PO-Phase-3-Study-for-Tebipenem-HBr-Stopped-Early-for-Efficacy-Following-Review-by-Independent-Data-Monitoring-Committee.html
2. Carreno JJ, et al. Longitudinal, Nationwide, Cohort Study to Assess Incidence, Outcomes, and Costs Associated With Complicated Urinary Tract Infection. Open Forum Infect Dis. 2019;6:ofz446.
3.Sabih A, Leslie SW. Complicated Urinary Tract Infections. [Updated 2024 Dec 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436013/
