A novel oral antibiotic called gepotidacin (Blujepa) has been approved by the U.S. Food and Drug Administration (FDA) to treat uncomplicated urinary tract infections (UTIs) among pediatric and female adult patients aged ≥ 12 years who weigh 40 kg or more. This drug is manufactured by GlaxoSmithKline (GSK) Pharmaceuticals Ltd. It acts against uncomplicated UTIs, targeting microorganisms such as Staphylococcus saprophyticus, Citrobacter freundii complex, Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae.
Gepotidacin is the first novel class of oral antibiotics for the treatment of UTIs in over 30 years. Gepotidacin was discovered by GSK scientists and is the first bactericidal antibiotic in the triazaacenaphthylene class. It targets the two different type II topoisomerase enzymes, which leads to the inhibition of bacterial deoxyribonucleic acid (DNA) replication.
UTIs occur most frequently among females. It affects approximately 16 million U.S. women yearly, with 30% experiencing recurrences that cause discomfort and disrupt daily life. There is a need for the discovery of innovative medicines in order to treat the growing number of UTIs caused by drug-resistant bacteria.
Thomas Hooton, MD, clinical medicine professor at the University of Miami School of Medicine, stated, “uUTIs can be a burden that seriously affects everyday activities. There is still a need for research on antimicrobial agents to address ongoing patient complications and the burden on the healthcare services, as more and more patients are experiencing recurrent infections.”
The pivotal phase 3 EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144) clinical trial results formed the basis for this approval. These studies evaluated the non-inferiority to nitrofurantoin of Blujepa in female adults and pediatric patients (Age = 12 years or more) with UTIs. All participants had a similar body weight of 40 kg or more.
In the EAGLE-2 study (n = 607; 1500mg gepotidacin group = 320 and 100mg nitrofurantoin group = 287), gepotidacin showed a therapeutic success rate of 50.6% for non-inferiority compared to 47.0% for nitrofurantoin with a covariate-adjusted treatment difference of 4.3% (95% confidence interval [CI], -3.6, 12.1).
In the EAGLE-3 trial (n = 541; 1500mg gepotidacin group = 277 and 100mg nitrofurantoin group = 264), gepotidacin was statistically significantly superior to nitrofurantoin, with 58.5% of patients experiencing therapeutic success compared to 43.6% for nitrofurantoin. The covariate-adjusted treatment difference was 14.6% (95% CI, 6.4, 22.8), and p = 0.0003.
The safety endpoints of Blujepa in this phase 3 clinical trial were consistent with previous clinical studies. The most common adverse events were gastrointestinal-related diarrhea, which occurred in 16% of patients, and nausea in 9% of the Blujepa group. The majority of events were mild (Grade 1), reported in 69% of participants, moderate (Grade 2) in 28%, and Grade 3 in 1%. Moreover, one drug-related serious adverse reaction was stated in each treatment group throughout the two clinical trials.
GSK-Chief Scientific Officer Tony Wood stated, “The approval is an important milestone because UTIs are among the most common infections in women. We are proud to have manufactured this drug for patients with recurrent infections and increasing resistance rates to available treatments.”
GSK intends to introduce gepotidacin for sale in the U.S. during the second half of 2025. Different government agencies, including the Defense Threat Reduction Agency, the US Department of Health and Human Services, and the Biomedical Advanced Research and Development Authority (BARDA), provided partial funding for the drug development process.
Reference: GSK. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older. Published March 25, 2025. Accessed March 26, 2025. Blujepa (gepotidacin) is approved by US FDA for the treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older
