GSK and Spero Therapeutics announced that the pivotal Phase III PIVOT-PO trial evaluating tebipenem HBr for complicated urinary tract infections (cUTIs) has been stopped early for efficacy. The decision followed a recommendation from an Independent Data Monitoring Committee (IDMC) based on a planned interim analysis of data from 1,690 patients enrolled in the study.
The trial successfully met its primary endpoint of non-inferiority of 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.
Addressing Critical Unmet Medical Need
If approved, tebipenem HBr would represent a significant advancement as the first oral carbapenem antibiotic for patients in the US who suffer from cUTIs. An estimated 2.9 million cases of cUTIs are treated annually in the US alone, with many cases requiring hospitalization and contributing to over $6 billion per year in healthcare costs.
"Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock," said Tony Wood, Chief Scientific Officer at GSK. "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. These positive results add to our growing anti-infectives portfolio and reinforce the potential of tebipenem HBr as an effective oral alternative taken at home."
Clinical Trial Design and Safety Profile
PIVOT-PO was a global, randomized, double-blind, pivotal Phase III clinical trial comparing oral tebipenem pivoxil HBr to IV imipenem in hospitalized adult patients with cUTI including pyelonephritis. Patients were randomized 1:1 to receive tebipenem pivoxil (600 mg) orally every six hours, or imipenem-cilastin (500 mg) IV every six hours, for a total of seven to ten days.
The IDMC review did not identify any new safety concerns beyond what has been reported in other studies with tebipenem, with diarrhea and headache as the two most reported adverse events.
Regulatory Timeline and Market Impact
GSK plans to work with US regulatory authorities to include the data as part of a filing in the second half of 2025. Full results will be submitted for presentation at an upcoming scientific congress and for publication in a peer-reviewed journal.
These infections are often caused by multidrug-resistant pathogens and carry increased risk of morbidity and mortality. Current standard of care includes carbapenem antibiotics, especially in cases of sepsis and allergies or resistance to other antibiotics, but they are only available for IV administration, resulting in significant emergency department visits and hospitalizations.
Development Partnership and Regulatory Status
The development of tebipenem HBr is supported in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA). In September 2022, GSK entered into an exclusive license agreement with Spero Therapeutics for the development and commercialization of tebipenem HBr in all markets, except certain Asian territories.
Tebipenem HBr has received Qualified Infectious Disease Product (QIDP) and Fast Track designations from the US FDA. This marks GSK's second anti-infective program to be stopped early for efficacy in Phase III, following the EAGLE 2 and EAGLE 3 trials for gepotidacin in 2022.
"We're proud of today's positive result for patients diagnosed with cUTI, including pyelonephritis, where oral treatments are much needed," said Esther Rajavelu, Chief Executive Officer of Spero Therapeutics. "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 PIVOT-PO trial to reach this advanced stage."
