Phase 3 Trial Shows Promise for Oral Antibiotic Tebipenem pivoxil hydrobromide in Treating Complicated UTIs

Topline results from the phase 3 PIVOT-PO trial have revealed that tebipenem pivoxil hydrobromide (HBr), an investigational oral carbapenem antibiotic, was evaluated in 1,690 adults with complicated urinary tract infections (cUTIs) or acute pyelonephritis. Participants were randomized to receive either oral tebipenem HBr or IV imipenem-cilastatin over 7 to 10 days, highlighting the potential of an effective oral treatment option for cUTIs.

The trial met the primary endpoint of non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized adult patients with cUTI, including pyelonephritis, on overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit. The IDMC review did not identify any new safety concerns beyond what has been reported in other studies with tebipenem, with diarrhea and headache as the two most reported adverse events. GSK plans to work with US regulatory authorities to include the data as part of a filing in 2H 2025. Full results will be submitted for presentation at an upcoming scientific congress and for publication in a peer-reviewed journal.

Esther Rajavelu, Chief Executive Officer, Spero, said: “Achieving the primary endpoint in the PIVOT-PO trial marks a significant milestone for tebipenem HBr. If approved, we believe tebipenem HBr is well positioned to change the treatment landscape for patients diagnosed with cUTI, including pyelonephritis. We look forward to working with GSK on next steps for this program, and would like to thank the patients, site investigators and other clinical staff, and Spero employees who worked diligently to help bring the product to this advanced stage.”

An estimated 2.9 million cases of cUTIs are treated annually in the US alone. These infections are often caused by multi-drug-resistant pathogens and carry increased risk of morbidity and mortality. Current standard of care includes carbapenem antibiotics, especially in case of sepsis and allergies or resistance to other antibiotics, but they are only available for IV administration. This results in significant emergency department visits and hospitalizations.

Tony Wood, Chief Scientific Officer, GSK, added: “Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock. Currently many need hospital-based intravenous treatment due to limited oral options for drug-resistant infections, contributing to over $6 billion per year in US healthcare costs2. These positive results add to our growing anti-infectives portfolio and reinforce the potential of tebipenem HBr as an effective oral alternative taken at home.”

About tebipenem HBr

Tebipenem pivoxil hydrobromide (HBr) is a late-stage development asset developed in collaboration with GSK. Tebipenem HBr is being developed to treat cUTIs, including pyelonephritis.

In September 2022, Spero entered into an exclusive license agreement with GSK for the development and commercialization of tebipenem HBr in all markets, except certain Asian territories. Under this agreement GSK has sub-licensed back to Spero Therapeutics the rights and responsibility to conduct certain development work including the PIVOT-PO Phase 3 trial, after which sponsorship of the new drug application (NDA) will be transferred to GSK from Spero Therapeutics. Tebipenem HBr has received Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA.

About PIVOT-PO

PIVOT-PO is a global, randomized, double-blind, pivotal Phase 3 clinical trial of oral tebipenem HBr versus IV imipenem cilastatin, in hospitalized adult patients with cUTI including pyelonephritis. Patients were randomized 1:1 to receive tebipenem HBr (600 mg) orally every six hours, or imipenem cilastatin (500 mg) IV every six hours, for a total of seven to ten days. The primary efficacy endpoint is overall response (composite of clinical cure plus microbiological eradication) at the test-of-cure visit. The primary analysis for the trial is an assessment of non-inferiority (NI) in the microbiological intention-to-treat population, based on a 10% NI margin. The trial enrolled a total of 1690 patients, with randomization stratified by age, baseline diagnosis (cUTI including pyelonephritis), and the presence or absence of urinary tract instrumentation.

About complicated urinary tract infections (cUTIs)

cUTIs are broadly described as any UTI that carries an increased risk of morbidity and mortality. Definitions of cUTIs are not currently uniform among international societies and regulatory agencies. cUTIs encompass a heterogeneous patient population due to the wide range of host factors, comorbidities and urological abnormalities associated with cUTIs.4,9 Risk factors for cUTI include indwelling catheters, ureteric stents, neurogenic bladder, obstructive uropathy, urinary retention, urinary diversion, kidney stones, diabetes mellitus, immune deficiency, urinary tract modification, and UTIs in renal transplant patients.