GSK and Spero Therapeutics Report Positive Phase 3 Results for Oral Antibiotic Tebipenem HBr

GSK and Spero Therapeutics have unveiled promising 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, demonstrate that the oral therapy closely matched the efficacy of the intravenous standard of care, potentially paving the way for a paradigm shift in cUTI treatment.

Trial Results and Implications

The phase 3 study, which was stopped early for efficacy in May, showed that tebipenem HBr was non-inferior to intravenous imipenem-cilastatin on the primary endpoint of clinical cure and microbiological eradication. Patients receiving 600 mg of tebipenem HBr achieved a 58.5% overall success rate, compared to 60.2% in the cohort receiving 500 mg of imipenem-cilastatin.

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. This finding could significantly influence the drug's potential clinical use, particularly in cases of resistant infections.

Regulatory Outlook and Market Potential

GSK, which acquired rights to tebipenem HBr in 2022 for $66 million upfront after an initial FDA rejection, plans to file for approval later this year. The successful phase 3 results mark a turning point for the once-rejected antibiotic and validate GSK's strategic investment.

If approved, tebipenem HBr could revolutionize cUTI treatment by enabling more patients to be treated outside of hospital settings. This shift could lead to significant cost savings for healthcare providers and improved patient experiences. However, questions remain about how the FDA will respond 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 competitive nature of this therapeutic area.

Basilea's chief medical officer, Marc Engelhardt, M.D., 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 potentially reduced concerns about resistance development associated with carbapenems.

As the pharmaceutical industry continues to address the urgent need for effective oral antibiotics, the success of tebipenem HBr represents a significant step forward in the treatment of complicated urinary tract infections and antimicrobial-resistant pathogens.