Zoliflodacin is an oral antibiotic that represents a novel class of antimicrobial agents called spiropyrimidinetriones.
Zoliflodacin (Nuzolvence) is a first-in-class oral antibiotic recently approved by the U.S. FDA for treating uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae, including strains resistant to some existing treatments.
It’s being developed primarily to treat gonorrhea, particularly strains that have become resistant to currently available antibiotics.
Gonorrhea has developed resistance to many standard antibiotics, and current first-line treatments often require injections (like ceftriaxone) plus oral azithromycin.
It works by inhibiting bacterial DNA gyrase (topoisomerase II), which is essential for DNA replication, but it binds to a different site than fluoroquinolone antibiotics, giving it activity against fluoroquinolone-resistant strains.
It shows promise in trials for uncomplicated urogenital gonorrhea, with single oral doses demonstrating effectiveness.
Its development of zoliflodacin is particularly important because Neisseria gonorrhoeae (the bacteria causing gonorrhea) has developed resistance to multiple antibiotic classes over time, and public health experts have been concerned about the potential for untreatable gonorrhea.
Indication: Treatment of uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 35 kg (about 77 lbs).
Oral suspension (granules that dissolve in water), given as a single 3 g dose.
Mechanism: It’s a spiropyrimidinetrione that inhibits bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) at a unique binding site, avoiding cross-resistance with many other antibiotics like fluoroquinolones.
Lab studies showed activity against multidrug-resistant strains.
A phase 3 randomized, open-label, non-inferiority trial involving 930 participants across sites in five countries (including the U.S., South Africa, Thailand, Belgium, and the Netherlands), .compared a single oral dose of zoliflodacin to the then-standard injectable ceftriaxone (500 mg) plus oral azithromycin.
Zoliflodacin was non-inferior (met efficacy goals) with high microbiological cure rates.
It had a similar safety profile to the comparator.