Gepotidacin Phase 3 Clinical Program Launches

GlaxoSmithKline (GSK) has launched a phase 3 clinical program for gepotidacin, a potential first-in-class antibiotic.

The candidate belongs to a new chemical class called triazaacenaphthylene bacterial topoisomerase inhibitors and will be investigated for treating uncomplicated urinary tract infections (UTIs) and urogenital gonorrhea. In the past 20 years, neither of the 2 infections have been addressed by new oral antibiotics.

According to a statement issued by GSK, gepotidacin works by interacting with 2 key bacterial enzymes that are responsible for bacterial replication—DNA gyrase and topoisomerase IV (type 2 topoisomerases). The dual targeting mechanism of action, which is reported to be distinct from all currently approved antibiotics, confers activity against pathogens that are resistant to currently available antibiotics, including fluoroquinolones.

The phase 3 development program will consist of 2 studies that will evaluate the candidate antibiotic in the 2 aforementioned infections which are caused by bacteria that are considered to be antibiotic-resistant threats by the US Centers for Disease Control and Prevention.

The Efficacy of Antibacterial Gepotidacin Evaluated (EAGLE) studies are being pursued following positive results in 2 phase 2 studies which evaluated the candidate for urogenital gonorrhea, and acute bacterial skin and skin structure infections (ABSSSI). The urogenital gonorrhea study demonstrated that a single, oral dose of gepotidacin was at least 95% effective for bacterial eradication of Neisseria gonorrhoea in adult participants. The ABSSSI study demonstrated that 2 of the 3 doses of gepotidacin tested met prespecified success criterial for the safety and efficacy profile.

The EAGLE-1 study will evaluate safety and efficacy will be evaluated for 3000mg of orally administered gepotidacin during baseline visit at the study site, followed by self-administration of a second oral dose as an outpatient 6 to 12 hours after the first dose. The candidate antibacterial will be compared to a single 500mg intramuscular dose of ceftriazone plus single 1g dose of oral azithromycin.

The study will enroll approximately 600 patients with uncomplicated urogenital gonorrhea caused by the bacterium N gonorrhoea. The study duration will be approximately 21 days and the primary end point will be the culture-confirmed bacterial eradication of the bacterial at test-of-cure visit.

EAGLE-2 will compare gepotidacin to nitrofurantoin in approximately 1200 adolescent and adult females with uncomplicated UTIs. Efficacy and safety of gepotidacin administered in 1500mg oral dose twice daily for 5 days will be compared to 100mg of nitrofurantoin administered in a 100mg oral dose twice daily for 5 days. The study duration will be approximately 28 days and the primary end point will be the therapeutic response at test-of-care visit in patients with qualifying uropathogens.

“Given the increasing rate of antibiotic drug resistance, and gepotidacin’s unique mechanism of action, we believe this drug has the potential to transform the treatment landscape for patients with uncomplicated urinary tract infection and urogenital gonorrhea who currently have limited therapeutic options,” Hal Baron, MD, chief scientific officer and president of research and development at GSK said in the company’s statement.

Gepotidacin has been developed in a public-private partnership between GSK, the Biomedical Advanced Research and Development Authority and Defense Threat Reduction Agency, in collaboration to develop antibiotics to fight antibiotic resistance and bioterrorism.