GSK Resubmits Tebipenem HBr NDA for Complicated UTIs After Phase 3 Non-Inferiority Data

GlaxoSmithKline resubmitted its new drug application for tebipenem HBr to the U.S. Food and Drug Administration on December 19, 2025, seeking approval to treat complicated urinary tract infections, including pyelonephritis. The resubmission was based on positive Phase 3 trial results demonstrating non-inferiority to intravenous imipenem-cilastatin, Spero Therapeutics said in a press release.

The resubmission follows a Complete Response Letter issued by the U.S. Food and Drug Administration in 2022, which required additional clinical trial data. The latest filing was supported by results from the Phase 3 PIVOT-PO trial (NCT06059846), which demonstrated that oral tebipenem HBr was non-inferior to intravenous imipenem-cilastatin in treating complicated urinary tract infections, including pyelonephritis, according to a December 19, 2025, press release from Spero Therapeutics. The trial, conducted under a Special Protocol Assessment, was stopped early in May 2025 due to efficacy observed at the planned interim analysis.

In the PIVOT-PO study, tebipenem HBr administered orally at 600 mg every six hours achieved an overall response rate of 58.5%, compared with a 60.2% response rate for intravenous imipenem-cilastatin dosed at 500 mg every six hours.

The primary endpoint was a composite measure of clinical cure and microbiological eradication at the test-of-cure visit, according to data presented jointly by Spero and GSK on October 21, 2025. The trial results were also presented as a late-breaking abstract at the IDWeek conference held October 19–22, 2025, in Atlanta, Georgia.

The NDA resubmission triggered a $25 million milestone payment from GSK to Spero Therapeutics, expected to be received in the first quarter of 2026, officials confirmed. Spero holds the exclusive license for tebipenem HBr outside certain Asian territories, while Meiji retains rights in select Asian regions, according to the licensing agreement disclosed by both companies. GSK is responsible for manufacturing, further development, and commercialization globally, except in the territories licensed to Meiji.

Tebipenem HBr has received Fast Track and Qualified Infectious Disease Product designations from the FDA, which could expedite the review process. Spero noted that the FDA’s regulatory decision on the resubmitted application is anticipated by March 26, 2026, though the agency may request additional data, potentially delaying approval beyond mid-2026. The PIVOT-PO trial was conducted with funding support from the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority under contract HHSO100201800015C, according to records.

If approved, tebipenem HBr would represent the first oral carbapenem antibiotic for complicated urinary tract infections, offering an alternative to intravenous therapy. Spero Therapeutics, which focuses on rare diseases and multi-drug resistant bacterial infections, will rely on GSK’s global commercialization capabilities for the product’s launch. The companies have reported mild adverse events in the trial, with no new safety concerns identified.

The FDA’s previous Complete Response Letter in 2022 had required additional clinical evidence, which the PIVOT-PO trial was designed to address under a Special Protocol Assessment agreement. GSK’s decision to resubmit the NDA follows the positive efficacy and safety data announced jointly with Spero in October 2025. Market analysts and industry sources note that the potential approval timeline aligns with GSK’s regulatory strategy and milestone expectations.

Spero Therapeutics’ stock price has remained near its 50-day average ahead of the FDA’s expected decision date. The companies continue to monitor the regulatory process closely, with GSK retaining discretion over further development and commercialization activities as stipulated in the licensing agreement.