GSK ends decades-long hiatus in oral antibiotics for UTIs

The FDA has approved GSK's gepotidacin, the first oral antibiotic to offer a new mechanism of action in uncomplicated urinary tract infections (uUTIs) in nearly 30 years, after a priority review.

The first in the new class of triazaacenaphthylene antibiotics has been approved under the Blujepa brand name to treat uncomplicated UTIs in adults and paediatric patients aged 12 and over. It can be used to treat infections caused by Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.

Gepotidacin inhibits DNA replication via two different type II topoisomerase enzymes, and its dual mode of action should make it harder for pathogens to develop resistance.

Its approval is a rare example of a new class of antibiotic reaching the market at a time when there is growing concern about the rising tide of antimicrobial resistance (AMR), which already kills a million and a half people every year worldwide and, according to some estimates,, could claim 10 million deaths a year by 2050.

"The approval of Blujepa is a crucial milestone with uUTIs among the most common infections in women," said GSK's chief scientific offer Tony Wood, pointing out that around 16 million women in the US are diagnosed with this sort of infection each year.

New treatments are needed as the number of uUTIs caused by drug-resistant bacteria is increasing, which can result in higher treatment failure rates. In the EAGLE-2 and EAGLE-3 trials that supported its approval, the antibiotic was found to be as effective as the go-to uUTI treatment nitrofurantoin, achieving numerically superior therapeutic success rates.

Primary care studies have suggested a worldwide failure rate of 10% to 18% with first-line therapies, and the consequences can be very serious, including kidney inflammation (pyelonephritis) and sepsis.

"We are proud to have developed Blujepa, the first in a new class of oral antibiotics for uUTIs in nearly three decades, and to bring another option to patients given recurrent infections and rising rates of resistance to existing treatments," he added.

Gepotidacin is also being developed for other problem infections, including uncomplicated urogenital gonorrhoea, and last year showed it was as effective as an intramuscular injection of ceftriaxone and oral azithromycin in the EAGLE-1 trial.

GSK is one of the few remaining big pharma companies carrying out R&D on new antibiotics, after a mass exodus from the category in the last few decades as companies struggled to get a return on R&D investment for drugs typically reserved for use when other therapies have failed.

Despite that, GSK has high hopes for Blujepa and two other anti-infective candidates in its pipeline – oral carbapenem antibiotic tebipenem and antifungal Brexafemme (ibrexafungerp) – and recently predicted peak sales of the three drugs could reach more than £2 billion a year. It is planning to launch Blujepa in the second half of this year in the US.

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