Key Takeaways
- GSK’s Blujepa was approved by the FDA for the treatment of uncomplicated UTIs, a valuable innovation in a condition facing threats from antibiotic resistance.
- Blujepa is first-in-class triazaacenaphthylene antibiotic, the first new mechanism of action for uUTIs in more than 30 years.
- Uncomplicated UTIs are the most common infection in women so Blujepa could address a substantial patient population.
GSK’s Blujepa (gepotidacin) is the first new mechanism of action to address uncomplicated urinary tract infections (uUTIs) in more than 30 years. The US Food and Drug Administration approved Blujepa on 25 March for female adults and pediatric patients 12 and older with uUTIs caused by Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus and Enterococcus faecalis.
Blujepa marks an important innovation in a therapeutic area that faces development and commercial challenges. Most drug makers have backed away from antibiotic drug development even as threats from antibiotic resistance continue to rise. Drug-resistant bacteria are increasingly responsible for uUTIs, which are the most common infection in women and affect 16 million women annually in the US alone, according to GSK.
Uncomplicated UTIs are bladder infections in otherwise healthy women, while complicated UTIs involve factors like pregnancy or other medical conditions.
GSK expects to launch Blujepa in the second half of the year and did not disclose pricing. Pricing is one of the challenges for newer antibiotics, which compete against readily available generic antibiotics. Novel medicines are also frequently held in reserve to address the most difficult infections, not only due to cost but also due to antibiotic stewardship.
In an email, the company described Blujepa as “a new oral treatment option for patients with uUTIs, particularly those at risk of treatment failure due to suspected resistance or a history of recurrence.”
“We are committed to working with healthcare providers and payers to support appropriate use,” the company added. However, GSK pointed out that the availability of Blujepa also allows for current antibiotics like sulfamethoxazole/trimethoprim, fluoroquinolones, and β-lactams to be reserved for the treatment of more serious infections.
A Novel Mechanism
Blujepa is first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication via a distinct binding site that for most pathogens provides inhibition of two different Type II topoisomerase enzymes. This provides activity against most target uropathogens (such as Escherichia coli and Staphylococcus saprophyticus), and Neisseria gonorrhoeae, including isolates resistant to current antibiotics, according to GSK. Due to its well-balanced inhibition of most pathogens, target-specific mutations in both enzymes are needed to significantly affect susceptibility to Blujepa, which is expected to reduce the potential for antibiotic resistance.
Blujepa was discovered by GSK scientists and developed in part with funding from the US Department of Health and Human Services, Administration for Strategic Preparedness and Response (ASPR) and Biomedical Advanced Research and Development Authority (BARDA).
The approval is based on the pivotal Phase III EAGLE-2 and EAGLE-3 trials, which demonstrated non-inferiority to nitrofurantoin, one of the leading standard of care antibiotics used for uUTI. In EAGLE-2, Blujepa demonstrated non-inferiority in therapeutic success, which occurred in 50.6% of participants compared to 47% for nitrofurantoin. In EAGLE-3, Blujepa demonstrated statistically significant superiority versus nitrofurantoin, with therapeutic success occurring in 58.5% of participants compared to 43.6%.
GSK also ran a successful Phase III trial, EAGLE-1, in uncomplicated urogenital gonorrhea (uCG), showing two oral doses of gepotidacin were non-inferior to a regimen of injected ceftriaxone with oral azithromycin. The company is planning a regulatory filing in uCG in the first half of the year, with a potential regulatory decision expected before the end of the year.
The company also has tebipenem pivoxil in Phase III development for complicated UTI, an oral carbapenem antibiotic licensed from Spero Therapeutics in 2022 for $66m upfront.