Data sets up filing of new GSK antibiotic this year

In a second piece of good news in the development of new antimicrobials this week, GSK has said it will file its oral carbapenem antibiotic tebipenem HBr for approval before the end of this year after a pivotal study was stopped early.

The phase 3 PIVOT-PO study, comparing tebipenem to an intravenous carbapenem regimen (imipenem and cilastatin) in people with complicated urinary tract infections (cUTIs), including pyelonephritis, was unblinded on the recommendation of its independent data monitoring committee after it became clear GSK's drug was at least as effective.

If approved, tebipenem could become the first oral carbapenem antibiotic for cUTIs in the US, providing a simple therapy for drug-resistant infections that can be treated at home rather than needing IV treatment in hospital, where patients can be at risk of contracting other infections.

It is the second FDA approval in cUTI in a matter of weeks, coming after GSK's triazaacenaphthylene drug gepotidacin became the first oral antibiotic with a new mechanism of action to be cleared for these infections in nearly three decades, and also follows the news this week that Roche is advancing novel antibiotic zosurabalpin into phase 3 for another serious, carbapenem-resistant Gram-negative infection.

Tebipenem was originally being developed by Spero Therapeutics, which filed for approval of the drug on the back of one trial (ADAPT-PO), only to have its application turned down by the FDA in 2022 with a request for a second study.

GSK paid $66 million upfront to license rights to tebipenem later that year, promising another $150 million on completion of the PIVOT-PO trial and $150 million on the first sale of the drug in the US or Europe. Shares in Spero rose nearly 250% after the latest study's termination was announced.

ADAPT-PO compared the drug to IV ertapenem in patients with cUTI and acute pyelonephritis, and PIVOT-PO's protocol was designed based on feedback from the US regulator.

An estimated 2.9 million cases of cUTIs are treated annually in the US, with many cases requiring hospitalisation, and it is estimated that the cost of caring for patients runs to around $6 billion per year.

"Complicated UTIs can have a profound impact on patients and carry a high risk of clinical complications, including sepsis and septic shock," said Tony Wood, GSK's chief scientific officer, who noted that many patients end up needing hospital-based IV treatment due to limited oral options for drug-resistant infections.

The company plans to work with the FDA to include the new data as part of a filing in the second half of this year.