Earlier this week, the FDA approved GSK’s antibiotic, gepotidacin (Blujepa). The treatment is indicated for uncomplicated urinary tract infections (UTIs) in female patients aged at least 12 years and weighing at least 40 kg, and that are caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis.1
Gepotidacin is a first-in-class triazaacenaphthylene antibiotic with a novel mechanism of action.1
“it actually prevents bactericidal DNA replication by 2 distinct enzymes. One is the DNA gyrase, and the other is topoisomerase 4,” said Pamela Kushner, MD, clinical professor of Family Medicine for the University of California at Irvine. “And this is a distinct mechanism of action because it interrupts the catalytic activity of the DNA gyrase and topoisomerase, and this is at an earlier stage than fluoroquinolones…There is also no overlap of the FQ binding sites, and that’s significant.”
The FDA approval was based on positive results from the pivotal phase 3 EAGLE-2 and EAGLE-3 trials which demonstrated noninferiority to nitrofurantoin, one of the leading current standard of care options for uUTI, in female adults (≥40 kg) and paediatric patients (≥12 years, ≥40 kg) with a confirmed uUTI. In EAGLE-2, gepotidacin demonstrated noninferiority in therapeutic success which occurred in 50.6% (162/320) of participants compared to 47.0% (135/287) for nitrofurantoin (covariate-adjusted treatment difference 4.3%, 95% CI (-3.6, 12.1)). 1
In EAGLE-3, gepotidacin demonstrated statistically significant superiority versus nitrofurantoin (one-sided p-value 0.0003). Therapeutic success occurred in 58.5% (162/277) of participants compared to 43.6% (115/264) for nitrofurantoin (covariate-adjusted treatment difference 14.6%, 95% CI (6.4, 22.8)). 1
“Both trials were identical, except for the collection of the PK data, which was only in EAGLE-2, and the post treatment EKGs, which was only in EAGLE-3,” Kushner said. “One of the most important things about this trial was that it was designed in accordance with the current FDA 2019 and EMA 2018 guidance for noninferiority and uncomplicated urinary tract infections…That’s a much more stringent criteria than was ever required before, and this is one of the first medications to be doing a study under these new criteria…Patients had to have a complete resolution of clinical symptoms, in addition to a reduction in qualifying your pathogens.”
Kushner appreciates the rigors of the trial standards, the patient populations that were studied, and now having a new first in-class antibiotic for this common infection.
“For clinicians, it gives us another option,” Kushner said. “I feel comfortable that the study involved so many patients over the age of 50; the fact that they had 40% of the patients who had some resistance to other antibiotics, and the fact that they had a higher test secure this is valuable to me. And as I said, unfortunately, our current antibiotics are having more and more resistance, and this is a problem that we can’t ignore.”
GSK is planning a US commercial launch in the second half of 2025.
