GSK will file oral carbapenem for complicated UTIs this year

GSK and Spero Therapeutics' oral cabapenem, tebipenem HBr, has become the first antibiotic in the class to show efficacy in a phase 3 trial involving patients with complicated urinary tract infections (cUTIs).

The results of the PIVOT-PO trial could reduce the need for patients with cUTIs to require treatment in hospital with intravenous carbapenems, raising patient convenience, reducing their risk of contracting other infections in hospital, and potentially reducing healthcare costs.

The two companies say they are now preparing to file for approval of the antibiotic before the end of the year.

The study compared tebipenem to a standard therapy of IV imipenem-cilastatin for cUTIs, including pyelonephritis, and showed that the two regimens were equally effective at achieving a clinical cure and eradicating the bacteria causing the infection, with a rate of 58.5% and 60.2%, respectively.

Microbiological response rates were 60.3% in the tebipenem group and 61.3% in the comparator arm, and were similar between patients with infections caused by antimicrobial-resistant (AMR) Enterobacterales – deemed by the WHO to be a priority pathogen – and the overall study population.

The safety profile of tebipenem was generally similar to that of imipenem-cilastatin and other carbapenem antibiotics, with the most frequently reported adverse events being diarrhoea and headache, cases of which were all mild or moderate and non-serious.

The data have been presented for the first time at the IDWeek infectious diseases conference in Atlanta, Georgia, after PIVOT-PO was halted early on the advice of its data monitoring committee earlier this year.

There are estimated to be around 29 million cUTI cases in the US alone every year, many of which are caused by multidrug-resistant (MDR) pathogens, and can result in organ failure, sepsis, and death. According to GSK, cUTIs cost US health systems around $6 billion a year to manage, with emergency department visits and hospitalisations a significant contributor.

Tebipenem was originally filed by Spero for cUTIs on the back of one trial, called ADAPT-PO, but had 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 were up more than 15% in premarket trading following the presentation of the data at IDWeek.

The company's chief executive, Esther Rajavelu, said the results of the study are "the culmination of years of dedicated work by our team in close collaboration with GSK," adding: "We are now focused on advancing tebipenem HBr toward FDA submission and bringing this important therapy to patients in need."

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