FDA set to decide on GSK's gepotidacin antibiotic in March
The FDA has started a priority review of GSK's gepotidacin, which could become the first in a new class of oral antibiotics for uncomplicated urinary tract infections (uUTIs) in over 20 years.
The US regulator is scheduled to deliver a decision on the marketing application by 26th March next year, said GSK in a statement.
Gepotidacin has an entirely new mechanism of action, inhibiting DNA replication via two different type II topoisomerase enzymes, which should make it harder for pathogens to develop resistance. It is the first in the new class of triazaacenaphthylene antibiotics.
Over half of all women are affected by uUTIs in their lifetime, with approximately 30% suffering from recurrent disease that can cause significant patient burden, including discomfort and restriction of daily activities, according to GSK.
At the same time, antimicrobial resistance (AMR) to common drugs used to treat these infections is on the rise, leading to treatment failure, with a Singapore study published last year finding resistance rates of 20% or more in Enterobacteriaceae pathogens treated with ciprofloxacin and co-trimoxazole.
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.
The FDA's review will focus on two phase 3 trials of gepotidacin in uUTIs – EAGLE-2 and EAGLE-3 – which were stopped early by their data monitoring committees after an interim look at the data showed clear efficacy and safety.
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.
AMR is a growing problem and one that is already claiming around 1.2 million lives per year globally. A recent study in The Lancet suggests that between 2025 and 2050 there could be 40 million direct deaths and 160 million indirect deaths as a result of AMR.
In September, world leaders meeting at the United Nations officially adopted a political declaration on the issue, which includes a target of a 10% cut in deaths related to AMR by 2030.
GSK, meanwhile, has also completed another phase 3 trial of gepotidacin, called EAGLE-1, which showed that two oral doses of the drug were as effective as a regimen based on an intramuscular injection of ceftriaxone and oral azithromycin in the treatment of urogenital gonorrhoea.
Gonorrhoea was diagnosed in 82 million people in 2020 and, according to World Health Organization (WHO) estimates, ranks high among the agency's infectious diseases of greatest concern, as it is rapidly becoming resistant to available antimicrobial medicines.
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.
The UK Government has made an effort to change that dynamic, launching a subscription payment model for new antibiotics that provides developers with a fixed annual access fee, regardless of how much is used to treat patients.
