Tebipenem HBr cUTI trial ends early after meeting efficacy goals

Tebipenem HBr cUTI trial ends early after meeting efficacy goals | Image Credit: © sopradit - © sopradit - stock.adobe.com.

The phase 3 PIVOT-PO trial, conducted to assess the impact of tebipenem HBr in patients with complicated urinary tract infections (cUTIs), will stop early for efficacy, according to GSK plc (LSE/NYSE: GSK) and Spero Therapeutics.¹

Potential first oral carbapenem option for cUTIs

Tebipenem HBr will be the first oral carbapenem antibiotic option against cUTIs for US patients if approved. This drug met the study’s primary endpoints of noninferiority compared to intravenous (IV) imipenem-cilastatin for treating cUTIs in adults. After this point, an Independent Data Monitoring Committee (IDMC) recommended the trial stop early for efficacy.

“We’re proud of today’s positive result for patients diagnosed with cUTI, including pyelonephritis, where oral treatments are much needed,” said Esther Rajavelu, Chief Executive Officer of Spero Therapeutics. “We look forward to working with GSK on next steps for tebipenem HBr.”

Challenges in defining and treating cUTIs

Patients with cUTIs face increased risks of morbidity and mortality. With no current uniform definition from regulatory agencies about the meaning of cUTIs, these conditions impact a heterogeneous patient population. Risk factors include ureteric stents, indwelling catheters, obstructive uropathy, neurogenic bladder, urinary diversion, urinary retention, and kidney stones.

Tebipenem was developed by GSK and Spero Therapeutics as a treatment method for patients with cUTIs. This drug has been evaluated in PIVOT-PO, a randomized, double-blind, pivotal phase 3 clinical trial. Participants included hospitalized adults with cUTIs, and the antibiotic was compared with IV imipenem among this population.

Patients were randomized to receive either tebipenem pivoxil 600 mg to take orally every 6 hours, or IV imipenem-cilastin 500 mg to take every 6 hours. Treatment occurred for 7 to 10 days, and blinding was achieved using matching placebos.

Primary outcomes and next steps

The overall response to treatment, defined as a composite of both clinical cure and microbiological eradication, was identified as the primary outcome. This was evaluated at the test-of-cure visit. There were 1690 patients included in the analysis, stratified based on age, baseline diagnosis, and urinary tract instrumentation presence.

Alongside meeting the primary endpoint, the IDMC did not find any new safety concerns for tebipenem, highlighting a consistent safety profile to those observed in previous clinical trials. Diarrhea and headache were reported as the 2 common adverse outcomes.

GSK has indicated it will include the data from the PIVOT-PO trial in a filing during the second half of 2025 with help from US regulatory authorities. Additionally, the company plans to present the full results at an upcoming scientific congress and to publish them in a peer-reviewed journal.

“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,” said Tony Wood, Chief Scientific Officer at GSK.

Recent FDA approval of enmetazobactam

Previously, the FDA approved enmetazobactam (Exblifep; Orchid Pharma) as a treatment option for adults with cUTIs.² This is a fourth-generation cephalosporin cefepime and proprietary beta lactamase inhibitor combination. In a phase 3 clinical trial, patients received enmetazobactam 0.5 g to be taken through 2 hours of intravenous infusion.

Results indicated a high success rate of 79.1% and treatment discontinuation of only 5.2%. This highlighted enmetazobactam’s potential as an additional cUTI treatment for US adults.

Reference

1. PIVOT-PO phase III study for tebipenem HBr stopped early for efficacy following review by Independent Data Monitoring Committee. GSK. May 28, 2025. Accessed May 28, 2025. https://www.gsk.com/en-gb/media/press-releases/pivot-po-phase-iii-study-for-tebipenem-hbr-stopped-early-for-efficacy-following-review-by-independent-data-monitoring-committee/.
2. Krewson C. FDA approves enmetazobactam for treatment of cUTIs. Contemporary OB/GYN. February 23, 2024. February 23, 2024. Accessed May 28, 2025. https://www.contemporaryobgyn.net/view/fda-grants-new-drug-approval-to-enmetazobactam-against-cutis.