FDA Approves GSK and Spero's Utebzi, First Oral Carbapenem Antibiotic in the US

GSK and Spero Therapeutics said on June 17 that the US Food and Drug Administration approved Utebzi (tebipenem pivoxil), an oral antibiotic for complicated urinary tract infections (cUTIs), including pyelonephritis, caused by certain susceptible bacteria in adults who have limited or no alternative oral treatment options, according to GSK's release. The companies said it is the first and only oral carbapenem antibiotic approved in the US for these patients.

Carbapenems are the standard treatment for severe or resistant infections but until now have been available only intravenously, GSK said. The approval covers infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca and Enterococcus faecalis.

The PIVOT-PO trial

The approval is supported by the Phase 3 PIVOT-PO trial (NCT06059846), a global, randomized, double-blind non-inferiority study in hospitalized adults with cUTI or acute pyelonephritis. It enrolled 1,690 patients, who received either 600 mg of oral tebipenem pivoxil or 500 mg of intravenous imipenem-cilastatin every six hours for seven to ten days.

On the primary endpoint, a composite of clinical and microbiological response at an assessment visit about 17 days after the first dose, tebipenem pivoxil achieved a 58.5% overall success rate (261 of 446 participants) compared with 60.2% (291 of 483) for imipenem-cilastatin, an adjusted treatment difference of -1.3% (95% CI, -7.5% to 4.8%) against a non-inferiority margin of -10%.

The trial was stopped early for efficacy after a planned interim analysis in May 2025, and its results were presented at IDWeek 2025 in October, Contagion Live reported. Response rates in participants with infections caused by antimicrobial-resistant Enterobacterales were consistent with the primary analysis, according to the outlet.

The most frequently reported adverse events, in at least 3% of patients, were diarrhea and headache, all mild or moderate and non-serious, GSK said.

"The approval of Utebzi provides the first and only oral carbapenem antibiotic for appropriate adults with complicated UTIs, a solution that could help reduce reliance on hospital-based intravenous care and support efforts to address resistant infections," said Tony Wood, GSK's chief scientific officer.

Path to approval

GSK licensed tebipenem from Spero in September 2022 for all markets except certain Asian territories, where Meiji retains rights, and later took over sponsorship of the new drug application. GSK resubmitted the application in December 2025, which triggered a $25 million milestone payment to Spero, and the user-fee goal date had been set for June 18, 2026, Contagion Live reported.

The drug holds FDA Qualified Infectious Disease Product and Fast Track designations, and its development was supported in part by federal funds from the Biomedical Advanced Research and Development Authority (BARDA). GSK said it expects tebipenem pivoxil to be available to US patients by the end of 2026.