GSK, Spero Therapeutics Oral UTI Treatment Trial Stopped Early for Efficacy

GSK and Spero Therapeutics announced on May 28, 2025, that a Phase III trial (PIVOT-PO)—evaluating the investigational oral treatment tebipenem HBr for complicated urinary tract infections (cUTIs), such as pyelonephritis—will be stopped early for efficacy based on the recommendation of an Independent Data Monitoring Committee (IDMC) (1). The IDMC review did not identify any new safety concerns beyond those identified in previous studies of tebipenem, with diarrhea and headache listed as the two most common adverse events.

The recommendation was based on a planned, interim data analysis of the nearly 1700 patients enrolled in the study (1). GSK said that the trial met the primary endpoint of non-inferiority of tebipenem HBr, compared with intravenous imipenem-cilastatin, in hospitalized adult patients with cUTIs including pyelonephritis.

A positive development

“We’re proud of today’s positive result for patients diagnosed with cUTI, includingpyelonephritis, where oral treatments are much needed,” Esther Rajavelu, chief executive officer of Spero Therapeutics, said in a GSK press 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 PIVOT-PO trial to reach this advanced stage.”

In the United States, an estimated 2.9 million cases of cUTIs are treated annually (1). The current standard-of-care includes intravenous carbapenem antibiotic treatment; if approved, tebipenem HBr would be the first oral carbapenem antibiotic available in the US.

“Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock,” Tony Wood, GSK chief scientific officer, said in the release (1). “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.”

GSK in the news

Developments on several other fronts at GSK were presented as part of the company’s exhibit at the American Thoracic Society International Congress, held in San Francisco from May 16–21, 2025 (2). This group of presentations, GSK said in a preview of the event, largely focused on optimal patient care that facilitates prevention and treatment of diseases such as asthma and chronic obstructive pulmonary disease.

GSK said it plans to work with US regulatory authorities to include the data from the PIVOT-PO trial, up to when it was stopped on the IDMC’s recommendation, later in 2025 (1). Full results are planned to be submitted for presentation at an upcoming scientific congress, and for publication in a peer-reviewed journal, but GSK did not specify in the press release which events or publications were being targeted.

References

1. GSK. PIVOT-PO Phase III Study for tebipenem HBr Stopped Early for Efficacy Following Review by Independent Data Monitoring Committee. Press Release. May 28, 2025.
2. GSK. GSK Continues to Advance the Future of Respiratory Medicine and Patient Care with New Data at ATS. Press Release. May 2, 2025.