Spero Therapeutics, GSK announce PIVOT-PO trial efficacy and safety results

Spero Therapeutics (SPRO) and GSK plc (GSK) announced efficacy and safety results of the phase 3 PIVOT-PO trial evaluating tebipenem HBr, an investigational oral treatment for complicated urinary tract infections, including pyelonephritis. These results were presented on October 20 in a late-breaking oral abstract session at IDWeek 2025 in Atlanta, Georgia. The trial, which was stopped early for efficacy in May this year, demonstrated non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis, based on the overall response at the test of cure visit. Tebipenem HBr achieved a 58.5% overall success rate compared to 60.2% overall success rate for imipenem-cilastatin. The safety profile of tebipenem HBr was generally similar to that of other carbapenem antibiotics. The most frequently reported adverse events were diarrhea and headache; these events were all mild or moderate and non-serious. Secondary endpoints also show: clinical cure rates at test of cure visit were 93.5% in the tebipenem HBr group compared to 95.2% in the imipenem-cilastatin group with adjusted treatment difference: -1.6%. Microbiological response rates at test of cure visit were 60.3% in the tebipenem HBr group compared to 61.3% in the imipenem-cilastatin group with adjusted treatment difference: -0.8%. Overall, clinical and microbiological response rates at test of cure in participants with infections caused by antimicrobial-resistant Enterobacterales were consistent with the respective response rates in the primary analysis population. Spero has licensed tebipenem HBr to GSK for development and commercialization in all markets except certain Asian territories. GSK plans to work with US regulatory authorities to include the data as part of a filing in Q4. If approved, tebipenem HBr would be the first oral carbapenem antibiotic in the US for patients who suffer from cUTIs, adding to GSK’s growing anti-infectives portfolio and helping address the challenges of antimicrobial resistance. 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.