GSK plc (LSE/NYSE: GSK) has unveiled encouraging outcomes from the pivotal EAGLE-1 phase III trial concerning gepotidacin, a prospective first-in-class oral antibiotic offering a novel approach to combat uncomplicated urogenital gonorrhoea (GC) in adolescents and adults. These findings are slated for presentation on April 30, 2024, at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global in Barcelona, Spain.
The EAGLE-1 trial’s primary endpoint focused on microbiological response, assessing the success or failure of eradicating the bacterial cause of gonorrhoea at the Test-of-Cure (ToC) visit occurring 3-7 days post-treatment. Results indicate gepotidacin (administered orally in two 3,000mg doses) to be non-inferior, boasting a success rate of 92.6% compared to 91.2% for the combination therapy of intramuscular (IM) ceftriaxone (500mg) and oral azithromycin (1,000mg), a leading regimen for gonorrhoea treatment.
During the EAGLE-1 trial, gepotidacin demonstrated a safety and tolerability profile consistent with earlier phase I and II trials. The most commonly reported adverse events (AEs) among gepotidacin recipients were gastrointestinal (GI) in nature. Notably, all AEs were mild or moderate (Grade 1 or 2), except for one severe (Grade 3) unrelated event in each treatment arm, alongside one unrelated serious event in the gepotidacin arm.
With an estimated 82 million new gonorrhoea cases reported globally each year, and a striking 118% increase in reported gonorrhoea rates in the United States from 2009 to 2021, innovative treatments are imperative, especially amid rising antibiotic resistance. Chris Corsico, SVP Development at GSK, emphasized the significance of gepotidacin’s potential as a new oral treatment option to address this growing concern, affirming GSK’s commitment to collaborating with global health regulators to introduce this prospective antibiotic.
Gonorrhoea, caused by the bacterium Neisseria gonorrhoeae, poses a significant public health threat, recognized as a priority pathogen by the World Health Organization. Its untreated consequences include infertility and other sexual and reproductive health complications, alongside heightened susceptibility to HIV infection.
Beyond its application in gonorrhoea, GSK is exploring gepotidacin’s potential in treating uncomplicated urinary tract infections (uUTI). Positive phase III data from the EAGLE-2 and EAGLE-3 trials, presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in April 2023 and published in The Lancet, underscore the broader therapeutic potential of gepotidacin. Notably, gepotidacin could represent the first oral antibiotic in over two decades for uUTI if approved, marking a significant milestone.
It’s noteworthy that the development of gepotidacin has received support from federal funds, underscoring its importance in addressing public health challenges.
Gepotidacin, a product of GSK’s research efforts, stands out as an investigational bactericidal antibiotic with a novel mechanism of action. Its inhibition of bacterial DNA replication through a unique binding site and mechanism of action provides broad-spectrum activity against various pathogens, including N. gonorrhoeae and certain antibiotic-resistant strains. GSK’s longstanding commitment to infectious disease innovation, coupled with its diverse pipeline of medicines and vaccines, positions the company as a leader in combating antimicrobial resistance.
In addition to gepotidacin, GSK’s strategic collaborations further reinforce its dedication to addressing infectious diseases. Exclusive license agreements for late-stage antibiotics and antifungal treatments demonstrate GSK’s multifaceted approach to meeting global health challenges.
