Blujepa (gepotidacin) / GSK - LARVOL DELTA

Blujepa (gepotidacin) approved by US FDA as oral option for treatment of uncomplicated urogenital gonorrhoea (uGC) (GSK Press Release) - "The US application was based on positive results from the EAGLE-1 phase III trial which demonstrated that gepotidacin was non-inferior to standard of care combination treatment for gonorrhoea (intramuscular ceftriaxone plus oral azithromycin)."

FDA approval • Infectious Disease

Pharmacokinetic and pharmacodynamic characterization of gepotidacin against Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh infection model. (PubMed, Antimicrob Agents Chemother) - "As previously reported, the systemic targets determined from PK/PD studies were applied to urine concentrations for probability of target attainment analyses, which led to successful clinical trials and regulatory approval for gepotidacin in the treatment of uUTI. However, further work is needed to confirm the translational validity of these approaches on a broader scale and their application in establishing PK/PD targets for cystitis."

Journal • PK/PD data • Preclinical • Infectious Disease • Nephrology • Pneumonia

Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity. (PubMed, Commun Biol) - "It targets both DNA gyrase and topoisomerase IV with balanced low-nanomolar potencies, showing remarkable superiority over ciprofloxacin and gepotidacin. The compound also demonstrates more than 5000-fold selectivity for bacterial over human topoisomerases and retains efficacy against fluoroquinolone and carbapenem-resistant clinical isolates. Together, these structural, biochemical, and microbiological insights elucidate BWC0977's broad-spectrum antibacterial activity and reduced vulnerability to resistance, establishing it as a promising next-generation antibiotic to address the global threat of antimicrobial resistance."

Journal • Infectious Disease • Pneumonia

Oral gepotidacin for the treatment of uncomplicated urinary tract infection in Japanese female patients: a randomized, active reference, double-blind, double-dummy, Phase 3 trial (EAGLE-J). (PubMed, J Infect Chemother) - P3 | "Gepotidacin therapeutic success at test-of-cure was consistent between EAGLE-J and EAGLE-2/-3. Gepotidacin has potential as a valuable oral treatment option for uUTI in Japan. No new safety signals were identified."

Clinical • Journal • P3 data • Infectious Disease • Nephrology

New Era for Urinary Tract Infection Treatment: Gepotidacin Receives FDA Approval. (PubMed, Int Urogynecol J) - No abstract available

FDA event • Journal • Infectious Disease • Nephrology

Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting against Neisseria gonorrhoeae Gyrase and Topoisomerase IV in Cells and In Vitro. (PubMed, ACS Infect Dis) - "Finally, mutations in aspartic acid residues predicted to mediate important gepotidacin-protein interactions in N. gonorrhoeae gyrase (GyrAD90) and topoisomerase IV (ParCD86) markedly diminished the activity of gepotidacin against the respective enzymes. Our findings differentiate gepotidacin targeting and mechanism from those of fluoroquinolones and highlight its potential to combat drug-resistant gonorrhea."

Journal • Preclinical • Infectious Disease • CD86

Antimicrobial potential of compounds from the MMV pandemic response box and COVID box against carbapenem-resistant Acinetobacter baumannii. (PubMed, Braz J Microbiol) - "Additionally, their effects on biofilm inhibition, protein leakage, and synergy with meropenem were assessed. Among the tested compounds, 10 demonstrated notable antimicrobial activity, including doxycycline, atazanavir, alexidine, eravacycline, erythromycin, gepotidacin, trimetrexate, MMV1634402 (brilacidin), MMV1580854 and MMV1578564...The present study highlights the antimicrobial activity of MMV1634402 (brilacidin) and gepotidacin, providing preliminary evidence of their potential as therapeutic candidates against CRAB. However, further studies involving a broader range of isolates and clinical validation are essential to confirm their efficacy and safety."

Journal • Infectious Disease • Malaria • Novel Coronavirus Disease

Antimicrobial resistance in Neisseria gonorrhoeae in nine sentinel countries within the World Health Organization Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), 2023: a retrospective observational study. (PubMed, Lancet Reg Health West Pac) - "Minimum inhibitory concentrations (MICs, mg/L) values were determined for ceftriaxone, cefixime, azithromycin, gentamicin, and ciprofloxacin using Etest (bioMérieux). Novel antimicrobials for gonorrhoea treatment are critical; zoliflodacin and gepotidacin are promising. WHO, Global Fund."

Journal • Observational data • Retrospective data • Infectious Disease

Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including subsets with molecularly characterized resistance mechanisms and genotypes/epidemiological clones, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3). (PubMed, Antimicrob Agents Chemother) - P3 | "Gepotidacin, a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial, was noninferior to nitrofurantoin in two pivotal trials (EAGLE-2 and EAGLE-3) in females with uncomplicated urinary tract infections (uUTIs). These data show gepotidacin's efficacy and in vitro activity against a wide range of uropathogen genotypes. Additionally, these pooled results provide a robust, contemporary data set and insight into current genotypic mechanisms of resistance.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04020341 and NCT04187144."

Journal • P3 data • Preclinical • Infectious Disease • Nephrology • Pneumonia

Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including drug-resistant phenotypes, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3). (PubMed, Antimicrob Agents Chemother) - P3 | "Two recent Phase 3 trials demonstrated the efficacy of gepotidacin compared with nitrofurantoin to treat uncomplicated urinary tract infections (uUTIs) in females...Among 1,159 E. coli isolates, 28%, 28%, 15%, and 28% were fluoroquinolone resistant (FQ-R), trimethoprim-sulfamethoxazole resistant (SXT-R), extended-spectrum β-lactamase positive (ESBL+), and multidrug resistant (MDR), respectively...Gepotidacin's efficacy, based on therapeutic, clinical, and microbiological success rates, was generally consistent across phenotypic subgroups of E. coli, K. pneumoniae, and P. mirabilis. This pooled analysis represents a robust, contemporary, clinically relevant, and unbiased (i.e., baseline urine specimens obtained from all enrolled participants regardless of uUTI history) collection of data from community-acquired uUTIs in females.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04020341 and NCT04187144."

Journal • P3 data • Preclinical • Infectious Disease • Nephrology • Pneumonia

An evaluation of antibiotic options for the treatment of biothreat pathogens. (PubMed, Front Antibiot) - "This review includes finafloxacin, levofloxacin, delafloxacin, omadacycline, gepotidacin, tebipenem and sulopenem. The selection criteria of these antibiotics were 1) the availability of an oral formulation, 2) the regulatory status (licensed by a regulatory authority or in an advanced stage of development) and 3) the availability of publicly available information on the biodefence pathogens of concern. We hope to highlight approved or advanced clinical candidates that have significant and unique potential in the biodefense space which may be deployed to protect both the public and warfighter against these bacterial infections."

Journal • Review • Infectious Disease

Analysis of MIC and Disk Diffusion Testing Variables for Gepotidacin and Levofloxacin against Gram-Positive and Gram-Negative Isolates (IDWeek 2025) - No abstract available

Gram negative • Gram positive • Infectious Disease

In vitro Activity of Gepotidacin and Comparator Agents Against a Collection of Escherichia coli and Klebsiella pneumoniae Urine Isolates From the United States During 2023 (IDWeek 2025) - No abstract available

Preclinical • Infectious Disease

Gepotidacin activity against Escherichia coli and Klebsiella pneumoniae, including molecularly characterized fluoroquinolone not susceptible subsets causing urinary tract infections in United States Medical Centers (2023) (IDWeek 2025) - No abstract available

Infectious Disease

Gepotidacin activity against Escherichia coli and Klebsiella pneumoniae, including molecularly characterized ESBL- and carbapenemase-positive subsets causing urinary tract infections in United States Medical Centers (2023) (IDWeek 2025) - No abstract available

Infectious Disease

Gepotidacin vs Standard Antibiotics: A Systematic Review and Meta-Analysis of Efficacy and Safety in Urogenital Infections (IDWeek 2025) - No abstract available

Retrospective data • Review • Infectious Disease

Well-Balanced Dual-Targeting of Gepotidacin against Neisseria gonorrhoeae Gyrase and Topoisomerase IV in Cells and in vitro (IDWeek 2025) - No abstract available

Preclinical • Infectious Disease

A Phase 3b, Open-label, Single-arm Study in Adolescent and Adult Female Participants to Evaluate Clinical Symptom Improvement and Safety of Gepotidacin During Treatment of Uncomplicated Urinary Tract Infections (uUTIs) (IDWeek 2025) - No abstract available

Clinical • P3 data • Infectious Disease

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved gepotidacin (Blujepa), a new kind of oral antibiotic pill to treat uncomplicated urinary tract infections (UTIs) in females aged 12 years and older, weighing at least 40 kg. (GOV.UK) - "The MHRA’s national approval is supported by evidence from two multicentre, randomised, active-controlled Phase 3 trials in females with uncomplicated UTIs, where 1572 participants were given gepotidacin and 1564 received nitrofurantoin, the frontline antibiotic currently used to treat uncomplicated UTIs."

MHRA approval • Infectious Disease

Gepotidacin accepted for priority review by US FDA for treatment of uncomplicated urinary tract infections in female adults and adolescents (GSK Press Release) - "...assigned a Prescription Drug User Fee Act (PDUFA) action date of 26 March 2025....The NDA is supported by positive results from the pivotal phase III EAGLE-2 and EAGLE-3 trials."

FDA filing • PDUFA • Priority review • Infectious Disease

Gepotidacin: First Approval. (PubMed, Drugs) - "In March 2025, gepotidacin was approved for the treatment of uUTIs caused by susceptible isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis in female adult and paediatric patients aged ≥ 12 years and weighing ≥ 40 kg in the USA. This article summarizes the milestones in the development of gepotidacin leading to this first approval for the treatment of bacterial uUTIs."

Journal • Infectious Disease • Nephrology • Pediatrics • Pneumonia

In urogenital gonorrhea, gepotidacin was noninferior to ceftriaxone + azithromycin for microbiological success. (PubMed, Ann Intern Med) - "GIM/FP/GP: [Formula: see text] Infectious Disease: [Formula: see text]."

Journal • Infectious Disease

Nephrotoxicity of New Antibiotics: A Systematic Review. (PubMed, Toxics) - "The agents assessed included aztreonam/avibactam, cefepime/enmetazobactam, cefiderocol, ceftobiprole, contezolid, gepotidacin, imipenem/cilastatin/relebactam, lascufloxacin, lefamulin, levonadifloxacin, plazomicin, and sulbactam/durlobactam. There is a need for post-marketing studies to better characterize renal safety. Clinicians should remain vigilant and continue to monitor for and report renal-related adverse events."

Journal • Review

TXA15054 - A Novel Narrow Spectrum Oral Antibiotic Against Neisseria Gonorrhoeae (ASM Microbe 2025) - "In this context, TAXIS Pharmaceuticals has successfully developed novel narrow spectrum inhibitors that specifically target bacterial dihydrofolate reductase (DHFR) while avoiding any significant engagement with human-DHFR (3).While inactive against other Gram-positive and Gram-negative pathogens, TXA15054 is potent against multiple Neisseria gonorrhoeae (Ng) strains, including ceftriaxone-resistant strains (WHO-X, WHO-Y, WHO-Z), azithromycin-, ciprofloxacin-, and tetracycline-resistant CDC isolates, with impressive low MIC values ranging from 0.031 to 0.004 μg/mL...TXA15054 showed minimal impact against Lactobacillus species in the urogenital tract unlike ceftriaxone, azithromycin and clinical trial candidates, zoliflodacin and gepotidacin...Cell. 2020 Jun 25; 181(7):1518-1532."

Infectious Disease • Vaginitis • DHFR

Potential of Established and Novel Antibacterials Against Acinetobacter baumannii Gyrase and Topoisomerase IV (ASM Microbe 2025) - "Thus, we assessed the effects of two novel antibacterials, gepotidacin (a triazaacenaphthelene, TAA) and zoliflodacin (a spiropyrimidinetrione, SPT), on the activities of the A. baumannii type II topoisomerases. Finally, gepotidacin displayed potent inhibition of the catalytic activity of both WT and mutant gyrase/topoisomerase IV (IC50: WT gyrase ≈ 0.9 µM, GyrAS80L ≈ 0.3 µM, WT topo IV ≈ 0.4 µM; ParCS84L ≈ 0.06 µM). Results suggest that these new classes of antibacterials maybe useful for treating FQ-resistant A. baumannii infections."

Infectious Disease