GSK's Oral Antibiotic Shows Promise in Phase 3 Trial for Complicated Urinary Tract Infections

GSK and Spero Therapeutics have unveiled positive phase 3 results for their oral antibiotic candidate, tebipenem HBr, in the treatment of complicated urinary tract infections (cUTIs). The data, presented at ID Week 2025 in Atlanta, demonstrates that the oral therapy closely matched the efficacy of the intravenous standard of care, potentially paving the way for a new treatment option that could reduce hospital stays and healthcare costs.

Pivotal Trial Results

The phase 3 study, which was stopped early for efficacy in May, evaluated tebipenem HBr against intravenous imipenem-cilastatin in hospitalized adults with cUTIs. The primary endpoint, assessing clinical cure and microbiological eradication, showed a 58.5% overall success rate for patients receiving 600 mg of tebipenem HBr, compared to 60.2% for those receiving 500 mg of imipenem-cilastatin. This difference fell within the trial's 10% margin for non-inferiority, successfully meeting the study's primary objective.

Secondary endpoints further supported the efficacy of tebipenem HBr:

• 93.5% of patients on tebipenem HBr were symptom-free, versus 95.2% on imipenem-cilastatin
• Microbiological response rates were 60.3% for tebipenem HBr and 61.3% for imipenem-cilastatin

Importantly, the efficacy of tebipenem HBr against antimicrobial-resistant Enterobacterales, including ESBL-producing strains and pathogens with limited susceptibility to levofloxacin, was consistent with the broader study population.

Regulatory Outlook and Market Potential

GSK, which acquired rights to tebipenem HBr from Spero Therapeutics in 2022 for $66 million upfront, plans to file for regulatory approval this year. The successful trial results come after an initial rejection by the FDA in 2022, which requested additional phase 3 data.

If approved, tebipenem HBr could significantly impact cUTI treatment by offering an effective oral alternative to intravenous therapies. This shift could potentially reduce hospitalizations and associated healthcare costs. However, questions remain about the FDA's response to a study that relied heavily on Eastern European trial sites, given the agency's emphasis on including U.S. patient data in regulatory submissions.

Competitive Landscape

The positive results for tebipenem HBr come amid growing interest in oral antibiotics for cUTIs. In August, Basilea Pharmaceutica licensed a phase 3-ready oral beta-lactam/beta-lactamase inhibitor from Venatorx Pharmaceuticals for up to $325 million, highlighting the potential market for these treatments.

Basilea's chief medical officer, Marc Engelhardt, has suggested potential advantages for their candidate over tebipenem HBr, including a lower dosing frequency (two to three times daily versus four times daily for tebipenem HBr) and potential differentiation in resistance profile.

As the pharmaceutical industry continues to seek innovative solutions for antibiotic-resistant infections, the development of effective oral therapies for cUTIs represents a significant step forward in addressing this critical medical need.