GSK preps filing for novel antibiotic for urinary tract infections

In an encouraging development for the fight against antimicrobial resistance (AMR), GSK’s novel antibiotic gepotidacin has shown efficacy in two phase 3 trials, setting up regulatory filings.

If approved, gepotidacin (GSK2140944) could become the first drug in a new class of oral antibiotics for uncomplicated urinary tract infections (UTIs) in more than 20 years, according to the pharma group, which plans to submit the data to the FDA in the first half of next year.

Crucially, gepotidacin has an entirely new mechanism of action, which should avoid resistance to current antibacterials, inhibiting DNA replication via two different type II topoisomerase enzymes which should make it harder for pathogens to develop resistance.

A study by the Pew Charitable Trust published in 2020 found that the triazaacenaphthylene drug was one of just three antibiotics in late-stage testing that offered a new and distinct mechanism of action.

The two phase 3 studies – called EAGLE-2 and 3 – were stopped early by their data monitoring committees after an interim look at the data showed clear efficacy and safety for GSK’s drug.

The studies involved more than 3,000 female adults and adolescents with uncompleted UTIs and showed that a five-day oral course of gepotidacin was as effective as standard therapy nitrofurantoin at achieving combined clinical and microbiological responses to the infection at 28 days.

Another study called EAGLE-1 is comparing two oral doses of gepotidacin to a regimen based on an intramuscular injection of ceftriaxone and oral azithromycin in the treatment of urogenital gonorrhoea.

According to GSK’s head of development Chris Crisco, uncomplicated UTIs are the most common outpatient infection affecting over half of all women during their lifetime, with more than a quarter of them suffering recurrent infections. The number of UTIs caused by resistant pathogens is also on the rise, he said.

“The…recommendation to stop the EAGLE-2 and 3 trials early for efficacy provides GSK with the opportunity to engage regulatory authorities as we work together to bring a new class of antibiotics to patients.”

AMR is a growing problem and one that is already claiming around 1.2 million lives per year globally and is expected to grow to 10 million by 2050 unless new drugs and other measures become available to control infections.

There are real concerns that we could be entering a post-antibiotic era, where even minor infections can be enough to kill patients. 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.

The main problem has been that investment in antibiotic development isn’t attractive, because novel drugs tend to be used sparingly, reserved for patients with MDR infections, so developers can’t make a return on their spend.

The pharma industry has taken other steps, including pooling R&D dollars to help support biotechs working in this area, for example, via the AMR Action Fund, which backed projects at Adaptive Phage Therapeutics (APT) and Venatorx Pharmaceuticals earlier this year.

In addition, there have been efforts to change the commercial model for antimicrobials to make developing them less risky.

The UK Government has made a play to change that dynamic, launching ‘Netflix-style’ subscription payments for new antibiotics, getting access in return for a fixed annual fee, regardless of how much is used to treat patients. The first drugs were included in that scheme earlier this year.

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