GSK/Spero: Utebzi (tebipenem pivoxil) approved in US for adults with cUTIs

Approval and indication

The US FDA approved Utebzi (tebipenem pivoxil) for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, in adults with limited or no alternative oral treatment options. The approval covers infections caused by specified susceptible pathogens: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis.

Clinical evidence

The approval is supported by the global PIVOT-PO phase III randomised, double-blind non-inferiority trial (NI margin −10%). Patients received oral tebipenem pivoxil 600 mg every six hours or IV imipenem-cilastatin 500 mg every six hours for seven to ten days. Tebipenem achieved a 58.5% overall success rate (261/446) versus 60.2% (291/483) for imipenem-cilastatin at the test-of-cure visit (adjusted treatment difference −1.3%; 95% CI −7.5%, 4.8%). The trial enrolled 1,690 participants with stratification by age, baseline diagnosis and instrumentation status.

Safety

The safety profile of tebipenem pivoxil was generally similar to imipenem-cilastatin and other carbapenems. The most frequently reported adverse events (≥3%) were diarrhoea and headache; these were described as mild or moderate and non-serious.

Market context and availability

There are more than 3 million cUTI cases in the US annually, with treatment failure affecting up to 34% of patients and substantial healthcare costs. Carbapenems are standard for severe or resistant infections but have been IV-only; an oral carbapenem could enable outpatient treatment. Tebipenem pivoxil is anticipated to be made available to US patients by the end of 2026.

Partnership and funding

The approval follows GSK’s development under an exclusive licence with Spero Therapeutics; the programme received partial federal funding from the US HHS/ASPR/BARDA under contract numbers HHSO100201800015C and HHSO100201300011C.