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A clinical trial shows tebipenem pivoxil hydrobromide (Tebipenem HBr; Spero Therapeutics and GSK) effectively treats complicated urinary tract infections (cUTIs), potentially transforming patient care and reducing hospital costs.
The pivotal phase 3 PIVOT-PO clinical trial (NCT06059846) evaluating tebipenem pivoxil hydrobromide (Tebipenem HBr; Spero Therapeutics and GSK), an investigational treatment for complicated urinary tract infections (cUTIs), met its primary end point and stopped early for efficacy, according to a news release. This decision was reported to have followed a recommendation from an Independent Data Monitoring Committee (IDMC).1,2
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Trial Name: 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 ID: NCT06059846
Sponsor: Spero Therapeutics
Completion Date: November 2025
“Achieving the primary end point in the PIVOT-PO trial marks a significant milestone for [tebipenem pivoxil hydrobromide]. If approved, we believe [tebipenem pivoxil hydrobromide] is well positioned to change the treatment landscape for patients diagnosed with cUTI, including pyelonephritis,” Esther Rajavelu, CEO of Spero Therapeutics, said in the news release.1
Tebipenem pivoxil hydrobromide is a late-stage agent under development for the treatment of cUTIs, including pyelonephritis, that are caused by certain bacteria. It is an oral formulation of tebipenem pivoxil, which is a carbapenem antibiotic of the β-lactam class. Previously, it received qualified infectious disease product and fast track designations from the FDA.1,3
cUTIs are broadly described as any UTI that carries an increased risk of either morbidity or mortality. Currently, definitions among international societies and regulatory agencies are not uniform. The infection encompasses a heterogeneous patient population because of the wide range of host factors, comorbidities, and urological abnormalities associated with cUTIs. Risk factors for cUTI include the following: indwelling catheters, ureteric stents, neurogenic bladder, obstructive uropathy, urinary retention, urinary diversion, kidney stones, diabetes, immune deficiency, urinary tract modification, and UTIs in patients following renal transplant.1
PIVOT-PO is a global, randomized, double-blind, double-dummy, multicenter, multinational phase 3 clinical trial assessing the efficacy of oral tebipenem pivoxil hydrobromide in hospitalized adult patients with cUTI, including pyelonephritis. A total of 1690 patients were randomly assigned to receive either 600 mg of oral tebipenem pivoxil hydrobromide and an intravenous (IV) dummy infusion (0.9% sodium chloride), or 500 mg of imipenem-cilastatin and matched oral dummy tablets. Both regimens were administered every 6 hours from days 1 through 10. Randomization was reported to be stratified by age, baseline diagnosis, and the presence or absence of urinary tract instrumentation.1,2
The primary end point was the number of participants with an overall response at the test-of-cure (TOC) visit, which was assessed on day 17. Secondary end points included the number of patients in the microbiologically evaluable population with overall, clinical, microbiological responses at the TOC, end-to-treatment, and late follow-up visits; the frequency of treatment-emergent and serious adverse events (AEs); and the plasma concentration of tebipenem pivoxil hydrobromide. Additionally, the primary analysis for the PIVOT-PO trial is an assessment of noninferiority that was based on a 10% noninferiority margin.1,2
The investigators reported that the trial had met its primary end point of noninferiority of tebipenem pivoxil hydrobromide compared with IV imipenem-cilastatin in hospitalized adults with cUTI (including pyelonephritis) on overall response at the TOC visit. The IDMC review reported that there were no new safety concerns observed beyond those reported in prior research. The most reported AEs were diarrhea and headache.1
“Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock. 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 health care costs,” Tony Wood, chief scientific officer, GSK, said in the news release. “These positive results add to our growing anti-infectives portfolio and reinforce the potential of [tebipenem pivoxil hydrobromide] as an effective oral alternative taken at home.”1
