FDA Approves Utebzi, the First Oral Carbapenem Antibiotic, for Complicated Urinary Tract Infections
GSK and Spero's tebipenem pivoxil becomes the first oral carbapenem cleared in the US, four years after an FDA rejection.
Overview
The US Food and Drug Administration approved Utebzi (tebipenem pivoxil) tablets on June 17, 2026, making it the first oral carbapenem antibiotic cleared for use in the United States, according to GSK. The drug is indicated for adults with complicated urinary tract infections (cUTIs), a class of infection that until now has typically required intravenous carbapenem therapy delivered in a hospital setting.
The approval caps a long regulatory road for tebipenem. When GSK and Spero Therapeutics first sought to bring an oral carbapenem to market, the drug “would be the first oral carbapenem antimicrobial to receive marketing approval in the United States,” the companies said when they announced their licensing agreement in 2022.
What We Know
Carbapenems are a class of antibiotics generally reserved for serious or drug-resistant infections, and they have historically been available only as intravenous formulations. Utebzi is an oral tablet, which means eligible patients could complete treatment without hospital-based IV care.
The approval is based on the Phase 3 PIVOT-PO trial. As GSK describes it, “The PIVOT-PO trial was a global, randomised, double-blind, pivotal, non-inferiority (NI margin: -10%) phase III trial evaluating the potential of oral tebipenem pivoxil compared to IV imipenem-cilastatin, in hospitalised adult patients with complicated urinary tract infections, including acute pyelonephritis.” Patients were randomized 1:1 to receive tebipenem pivoxil 600 mg orally every six hours, or imipenem-cilastatin 500 mg intravenously every six hours, for a total of seven to ten days, GSK said.
The trial’s efficacy and safety results, published in Open Forum Infectious Diseases, show the oral drug held up against the IV comparator. According to the PIVOT-PO publication, “Overall response at TOC was 58.5% in 261/446 participants who received TBP-PI-HBr versus 60.2% in 291/483 participants who received IMI-CIL (adjusted treatment difference: −1.3%; 95% CI: −7.5%, 4.8%).” The primary endpoint of overall response — a composite of clinical cure plus microbiological eradication — was assessed at the test-of-cure visit in the microbiological intent-to-treat population, and the study was stopped for efficacy, the authors reported. On safety, the publication notes that “The safety profile of TBP-PI-HBr was overall consistent with IMI-CIL; the two most frequent treatment-emergent adverse events were diarrhea and headache,” per the study authors.
The indication covers infections caused by specified pathogens. GSK lists them as Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis.
The company frames the approval against a backdrop of rising resistance and frequent treatment failure. “There are more than 3 million cases of cUTI in the US annually and treatment failure impacts up to 34% of patients,” GSK said. In a statement, Tony Wood, Chief Scientific Officer at GSK, said: “With antibiotic resistance continuing to rise, patients and healthcare professionals need new treatment options. 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.”
A Second Attempt After a 2022 Rejection
The approval arrives four years after the FDA first declined to clear the drug. On June 27, 2022, Spero Therapeutics received a Complete Response Letter for its tebipenem HBr New Drug Application for complicated urinary tract infection, including pyelonephritis. As Spero explained at the time, “the FDA ultimately concluded that Spero’s Phase 3 cUTI study of tebipenem HBr (ADAPT-PO) was insufficient to support approval and that additional clinical study would be required.”
“We are disappointed with the FDA’s decision, but we look forward to our continued dialogue, addressing the agency’s concerns and outlining a clear path forward for tebipenem HBr,” Ankit Mahadevia, M.D., Chief Executive Officer of Spero, said in the company’s announcement.
Later that year, GSK stepped in. The two companies announced an exclusive licensing agreement on 22 September 2022, with GSK paying “$66 million upfront.” The new PIVOT-PO trial provided the additional clinical evidence the agency had sought.
What We Don’t Know
GSK says Utebzi is “anticipated to be made available to US patients by the end of 2026,” according to the company, but pricing and the precise commercial launch date were not disclosed in the approval announcement. How quickly clinicians adopt an oral option in place of IV carbapenems — and how stewardship programs balance convenience against the goal of preserving last-line antibiotics — will become clearer only after the drug reaches the market.