Oral tebipenem HBr matches IV carbapenem in phase 3 cUTI trial

GSK and Spero Therapeutics announced full results from the pivotal phase 3 PIVOT-PO trial evaluating tebipenem hydrobromide (HBr), an investigational oral carbapenem antibiotic for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Findings were presented on October 20, 2025, during a late-breaking oral abstract session at ID Week 2025 in Atlanta, Georgia.¹

Complicated urinary tract infections account for an estimated 2.9 million cases annually in the United States and are frequently caused by multidrug-resistant pathogens. These infections carry increased risks of organ failure, sepsis, and death, and are associated with more than $6 billion in annual healthcare costs. Current treatment options for resistant cUTIs often involve intravenous (IV) carbapenem antibiotics, which require hospital administration.²

George Sakoulas, MD, adjunct professor in the Department of Pediatrics at the University of California San Diego School of Medicine and chief of infectious diseases at Sharp Rees Stealy Medical Group, stated, “Increasing antibiotic resistance among community-acquired bacteria that cause cUTIs is greatly amplifying the burden of treatment for patients, clinicians, and payers. The therapeutic flexibility of a new oral antibiotic may reduce the need for intravenous antibiotics to treat cUTI, providing benefit to patients and improving treatment options.”

Trial design and efficacy outcomes

The PIVOT-PO trial (NCT06059846) was a randomized, double-blind, global phase 3 study comparing oral tebipenem HBr (600 mg every 6 hours) with IV imipenem-cilastatin (500 mg every 6 hours) in hospitalized adults with cUTI or pyelonephritis. The trial was stopped early for efficacy in May 2025.

Tebipenem HBr demonstrated non-inferiority to imipenem-cilastatin based on overall response, defined as a composite of clinical cure and microbiological eradication at the test-of-cure visit. The oral tebipenem HBr group achieved a 58.5% overall success rate (261/446 participants) compared with 60.2% for imipenem-cilastatin (291/483 participants), with an adjusted treatment difference of −1.3% (95% CI, −7.5% to 4.8%).

Clinical cure rates—defined as the absence of symptoms—were 93.5% for tebipenem HBr and 95.2% for imipenem-cilastatin (adjusted difference, −1.6%; 95% CI, −4.7% to 1.4%). Microbiological response rates were 60.3% and 61.3%, respectively (adjusted difference, −0.8%; 95% CI, −6.9% to 5.3%). Infections caused by antimicrobial-resistant Enterobacterales demonstrated consistent response rates with the overall trial population.

Safety and tolerability

The safety profile of tebipenem HBr was generally comparable to imipenem-cilastatin and other carbapenems. The most common adverse events, occurring in at least 3% of participants receiving tebipenem HBr, were diarrhea and headache. All adverse events were mild or moderate and non-serious.

Expert and company perspectives

Tony Wood, chief scientific officer at GSK, stated, “Complicated UTIs can have serious consequences for patients, including organ failure and sepsis, and oral options for drug-resistant infections are limited. These ground-breaking data show for the first time that cUTIs, including pyelonephritis, can be treated with an oral carbapenem antibiotic as effectively as with an intravenous one. We have a long-standing commitment to delivering novel anti-infectives and are delighted to offer the potential of tebipenem HBr as an effective oral alternative that could be taken at home.”

Esther Rajavelu, CEO of Spero Therapeutics, commented, “These data presented at IDWeek represent the culmination of years of dedicated work by our team in close collaboration with GSK. We are deeply grateful to the physicians, researchers, support staff, and, most importantly, to the patients who made this study, and the ones before it, possible. Along with GSK, we are now focused on advancing tebipenem HBr toward FDA submission and bringing this important therapy to patients in need.”

Next steps and regulatory plans

GSK plans to include these data as part of a submission to the FDA in the fourth quarter of 2025. If approved, tebipenem HBr would become the first oral carbapenem antibiotic in the United States for patients with cUTIs.

Tebipenem HBr has received Qualified Infectious Disease Product and Fast Track designations from the FDA.

References

1. Positive PIVOT-PO phase III data show tebipenem HBr’s potential as the first oral carbapenem antibiotic for patients with complicated urinary tract infections (cUTIs). GSK. October 21, 2025. Accessed October 21, 2025. https://www.gsk.com/en-gb/media/press-releases/positive-pivot-po-phase-iii-data-show-tebipenem-hbr-s-potential-as-the-first-oral-carbapenem-antibiotic-for-patients-with-complicated-urinary-tract-infections-cutis/
2. Sabih A, Leslie SW. Complicated Urinary Tract Infections. [Updated 2024 Dec 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436013/