FDA approves Utebzi, first oral carbapenem antibiotic for complicated urinary tract infections in adults

New oral treatment could help eligible patients receive care outside hospital settings instead of relying on intravenous antibiotics

The US Food and Drug Administration (FDA) has approved Utebzi (tebipenem pivoxil), the first oral carbapenem antibiotic for adults with certain complicated urinary tract infections (cUTIs), creating a potential alternative to hospital-based intravenous treatment. The approval could enable more eligible patients to be treated outside hospital settings while receiving a class of antibiotics traditionally administered through an intravenous drip.

The approval covers the treatment of complicated urinary tract infections, including pyelonephritis, a kidney infection that can develop when a urinary tract infection spreads to the kidneys. Utebzi is approved for adult patients with infections caused by certain susceptible pathogens who have limited or no alternative oral treatment options.

The decision marks the first approval of an oral carbapenem antibiotic in the United States. Carbapenems are widely used to treat severe or antibiotic-resistant bacterial infections but have until now been available only through intravenous administration.

Need for new treatment options

According to GSK, more than three million cases of complicated urinary tract infections are treated annually in the United States. The company said treatment failure affects up to 34% of patients and that up to one-third of infections are caused by resistant pathogens.

Complicated urinary tract infections are often associated with multidrug-resistant bacteria, making them more difficult to treat. GSK said these infections account for more than $6 billion annually in healthcare costs in the United States.

Tony Wood, Chief Scientific Officer at GSK, said the approval comes at a time when antibiotic resistance continues to increase.

“With antibiotic resistance continuing to rise, patients and healthcare professionals need new treatment options,” Wood 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.”

Phase III trial results

The approval was supported by findings from the PIVOT-PO Phase III clinical trial.

A Phase III trial is a late-stage study conducted in a large group of patients to assess a treatment’s effectiveness and safety before regulatory approval.

The trial evaluated oral tebipenem pivoxil against intravenous imipenem-cilastatin in hospitalised patients with complicated urinary tract infections, including pyelonephritis.

The study demonstrated non-inferiority of tebipenem pivoxil compared with intravenous imipenem-cilastatin. Non-inferiority means the new treatment performed comparably to the existing standard treatment within a pre-specified margin.

Researchers assessed overall response at the test-of-cure visit, defined as a combination of clinical cure and microbiological eradication of the infection.

Potential to expand outpatient treatment

Dr Bilal Chughtai, Chief of Urology at Plainview Hospital, Northwell Health, and Associate Professor of Urology at the Zucker School of Medicine at Hofstra/Northwell, said the approval could reduce the burden associated with current treatment approaches.

“For patients with complicated urinary tract infections (cUTIs) and their caregivers, this approval is a major milestone as today’s standard of care places a serious burden on them and hospitals,” Chughtai said.

“A new effective oral treatment offering an alternative option to intravenous care has the potential to enable more treatment in the outpatient settings with the ambition to improve their experience.”

Safety findings

According to the trial results, the safety profile of tebipenem pivoxil was generally similar to that of imipenem-cilastatin and other carbapenem antibiotics.

The most commonly reported adverse events, occurring in at least 3% of patients, were diarrhoea and headache. These events were reported as mild or moderate and non-serious.

Collaboration between GSK and Spero

The approval follows a development and exclusive global licensing agreement between GSK and Spero Therapeutics, excluding select Asian territories.

Esther Rajavelu, President and Chief Executive Officer of Spero Therapeutics, said the approval represented the culmination of more than a decade of work on the programme.

“The FDA approval of tebipenem pivoxil marks the culmination of more than a decade of dedication from our team, partners, and, most importantly, the patients who placed their trust in this programme,” Rajavelu said.

“Through our partnership with GSK, we look forward to this much-needed oral treatment option reaching cUTI patients to help reduce the burden of the disease.”

GSK said Utebzi is expected to become available to patients in the United States by the end of 2026.