At IDWeek 2025, a major forum for infectious disease (ID) professionals to share science, collaborate and improve patient care which is taking place in Atlanta in the US state of Georgia from 19 to 21 October, Dr David Hong from Spero Therapeutics has shared efficacy and safety data from a Phase III randomised open-label non-inferiority study investigating oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) compared to a standard-of-care (SOC) therapy, intravenous (IV) imipenem-cilastatin (IMI-CIL), in hospitalised adult patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP).
cUTI is a common infection in the US, with around three million diagnosed cases a year. Due to the rise in antimicrobial resistance, the treatment of AP and cUTI with or without AP is becoming increasingly difficult. There is an unmet need for home-based treatment via preferred routes of administration. Hence, oral TBP-PI-HBr, an investigational oral carbapenem tablet with activity against antimicrobial-resistant enterobacterales, and some gram-positive pathogens, would be an ideal alternative treatment that could potentially reduce hospitalisations for cUTI and AP patients, and alleviate the burden of these infections on the healthcare system.
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The PIVOT PO trial (NCT06059846) included 929 hospitalised patients aged 18 or older with a clinical diagnosis of cUTI or AP. These patients were randomised into two groups: those receiving TBP-PI-HBr (oral 600mg + saline placebo IV) for seven to 10 days, and those receiving IMI-CIL (IV 500mg +oral placebo tablet) for seven to 10 days. Upon completion of the course, there was an end-of-study visit and seven days after this, the primary efficacy analysis was conducted during the test-of-cure visit.
The primary endpoint was the overall response at test-of-cure visit in the microbiological intent-to-treat population. This incorporated a clinical cure, defined as a complete resolution of clinically significant alleviation of baseline signs and symptoms of cUTI or AP, as well as microbiological eradication, defined as a reduction of baseline uropathogens to less than 10^3 CFU/mL, and a negative repeat blood culture if a culture was positive at baseline.
Baseline characteristics were balanced between treatment groups, with a mean age of 64.4 years, a baseline bacteremia average at 7.1%, and infection types split with 34.3% of patients having AP only, 22.3% of patients having cUTI with AP, and 43.4% of patients having cUTI without AP. In terms of baseline microbiology, Escherichia coli was the most common baseline qualifying uropathogen at 73.3%. 37% of patients had antimicrobial-resistant enterobacterales pathogens, and 47.6% had multi-drug-resistant pathogens present.
Trial results demonstrated that oral TBP-PI-HBr was non-inferior to IV IMI-CIL in the treatment of cUTI or AP and showed comparable efficacy in participants with ESBL+ enterobacterales, with no new safety signals identified. The response rate in the TBP-PI-HBr group was 58.5%, versus 60.2% in participants who received IMI-CIL (adjusted treatment difference −1.3%, 95% confidence interval [CI] −7.5%, 4.8%). Treatment effects were comparable in participants with ESBL+ enterobacterales. The safety profile of TBP-PI-HBr was overall consistent with IMI-CIL, with the two most frequent treatment-emergent adverse events being diarrhoea and headache.
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By GlobalDataClinical response remained high throughout the study in both groups, and microbiological response was comparable. Therefore, TBP-PI-HBr may provide an effective treatment option for cUTI or AP and address a significant unmet need, with potential to become the first oral carbapenem antibiotic for this market.
