FDA approves tebipenem pivoxil as first oral carbapenem antibiotic for complicated urinary tract infections

The FDA has approved tebipenem pivoxil (Utebzi; Spero Therapeutics/GSK) for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, making it the first oral carbapenem antibiotic available in the US for this indication. The approval offers a new treatment pathway for patients who have historically required intravenous (IV) therapy, particularly in cases involving drug-resistant pathogens.^1-3

“For patients with cUTIs and their caregivers, this approval is a major milestone as today’s standard of care places a serious burden on them and hospitals,” said Bilal Chughtai, Chief of Urology at Plainview Hospital, Northwell Health and Associate Professor of Urology at the Zucker School of Medicine at Hofstra/Northwell, in a statement.¹

“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,” added Chughtai.

Complicated UTIs represent a significant public health burden, with an estimated 2.9 million cases treated annually in the United States alone. These infections are frequently caused by multidrug-resistant pathogens and carry serious risks, including organ failure, sepsis, and death. They also contribute to substantial emergency department visits and hospitalizations, generating more than $6 billion per year in healthcare costs. The current standard of care has included carbapenem antibiotics in cases involving sepsis or resistance to other antibiotics, though until now these agents have only been available for IV administration.³

Phase 3 PIVOT-PO trial

The FDA approval is supported by results from the phase 3 PIVOT-PO trial (NCT06059846), which were presented as a late-breaking oral abstract at IDWeek 2025 in Atlanta, Georgia, on October 20, 2025.³ The trial was stopped early for efficacy following a planned interim analysis in May 2025.²

The trial demonstrated non-inferiority of tebipenem HBr compared to IV imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis, based on overall response, a composite of clinical cure plus microbiological eradication of the causative bacteria, at the test of cure visit. Tebipenem HBr (oral, 600 mg) achieved an overall success rate of 58.5% (261/446 participants) compared to 60.2% (291/483 participants) for imipenem-cilastatin (IV, 500 mg), with an adjusted treatment difference of 1.3% (95% CI: 7.5%, 4.8%).³

Secondary endpoint data further supported these findings:

• Clinical cure rates at the test of cure visit were 93.5% in the tebipenem HBr group (417/446) versus 95.2% in the imipenem-cilastatin group (460/483), with an adjusted treatment difference of 1.6% (95% CI: 4.7%, 1.4%)
• Microbiological response rates at the test of cure visit were 60.3% in the tebipenem HBr group (269/446) versus 61.3% in the imipenem-cilastatin group (296/483), with an adjusted treatment difference of 0.8% (95% CI: 6.9%, 5.3%)
• Clinical and microbiological response rates in participants with infections caused by antimicrobial-resistant Enterobacterales were consistent with the primary analysis population

Is tebipenem HBr safe?

The safety profile of tebipenem HBr was generally similar to that of other carbapenem antibiotics. The most frequently reported adverse events, occurring in 3% or more of patients who received tebipenem HBr, were diarrhea and headache, both of which were mild or moderate in severity and non-serious.

What led to the FDA approval of tebipenem HBr?

GSK filed the NDA resubmission with the FDA in December 2025, triggering a $25 million milestone payment to Spero Therapeutics.² The resubmission was supported by the PIVOT-PO trial results, which had been presented at IDWeek 2025 just weeks prior.² The PDUFA date was subsequently set for June 18, 2026.

Spero has granted GSK an exclusive license to commercialize tebipenem HBr in all territories except certain Asian territories, where Meiji retains development and commercialization rights.² If approved, tebipenem HBr would add to GSK's growing anti-infectives portfolio while addressing the ongoing challenges of antimicrobial resistance.³

References:

1. Utebzi (tebipenem pivoxil) approved in the US for adults with complicated urinary tract infections (cUTIs). GSK. News release. June 17, 2026. Accessed June 17, 2026. https://www.gsk.com/en-gb/media/press-releases/utebzi-tebipenem-pivoxil-approved-in-the-us-for-adults-with-complicated-urinary-tract-infections-cutis/
2. Spero Therapeutics Announces First Quarter 2026 Operating Results and Provides Business Update. Spero Therapeutics. News release. Published May 13, 2026. Accessed June 18, 2026. https://www.globenewswire.com/news-release/2025/12/19/3208446/0/en/Spero-Announces-NDA-Resubmission-of-Tebipenem-HBr-by-GSK-to-the-FDA-for-the-Treatment-of-Complicated-Urinary-Tract-Infections-Including-Pyelonephritis.html
3. PIVOT-PO Phase 3 Data Show Tebipenem HBr's Potential as the First Oral Carbapenem
   Antibiotic for Patients with Complicated Urinary Tract Infections (cUTIs). Spero Therapeutics. News release. Published October 21, 2025. Accessed June 18, 2026. https://s3.amazonaws.com/b2icontent.irpass.cc/2748/rl158673.pdf