FDA Accepts NDA for Zoliflodacin, Potentially First Gonorrhea Antibiotic in Decades

The FDA has accepted a New Drug Application (NDA) for zoliflodacin, an investigational oral antibiotic intended to treat uncomplicated gonorrhea in adults and adolescents ages 12 and older. The application acceptance was announced in a joint news release on June 10 by Innoviva Specialty Therapeutics Inc., the pharmaceutical company developing the treatment, and the Global Antibiotic Research & Development Partnership (GARDP), a nonprofit focused on combating drug resistant infections.

Zoliflodacin is a first in class spiropyrimidinetrione antibiotic that works by targeting type 2 topoisomerase, an essential bacterial enzyme. This mechanism of action is distinct from currently approved antibiotics, which may help reduce the likelihood of cross resistance.

The FDA has also granted zoliflodacin Qualified Infectious Disease Product (QIDP) status, which provides Priority Review and Extended Market Exclusivity under the Generating Antibiotic Incentives Now (GAIN) Act. This designation is designed to encourage the development of new antimicrobial drugs for serious or life threatening infections caused by resistant pathogens.

The NDA acceptance marks a significant milestone in the fight against antibiotic resistant gonorrhea, which has become increasingly difficult to treat with existing therapies. Zoliflodacin, if approved, would be the first in a new class of antibiotics for gonorrhea treatment in decades.

The NDA submission is supported by data from several clinical trials, including a pivotal phase 3 study involving 930 participants diagnosed with gonorrhea. In the trial, a single 3 g oral dose of zoliflodacin demonstrated a 90% cure rate. For comparison, an intramuscular injection of 500 mg of ceftriaxone plus a 1 g oral dose of azithromycin achieved a 96.2% cure rate. No serious adverse events or deaths were associated with zoliflodacin treatment, suggesting it may offer a safe and effective alternative, according to a separate news release.

The World Health Organization (WHO) has identified antimicrobial resistance as one of the top ten global public health threats, and Neisseria gonorrhoeae, the bacterium that causes gonorrhea, is a leading concern due to its ability to quickly develop resistance to antibiotics. Ceftriaxone, the backbone of current treatment protocols, has been in use since 1984 and has seen growing resistance in recent years. With no new antibiotics approved for gonorrhea in over a decade, zoliflodacin represents a potentially vital tool to address this escalating challenge.

Gonorrhea is the second most commonly reported bacterial sexually transmitted infection worldwide, following Chlamydia trachomatis. The WHO reports that more than 82 million cases occurred globally in 2020. The infection can affect the genitals, rectum, and throat and is often asymptomatic, especially in women. When symptoms do appear, they can mimic urinary tract infections or other conditions, complicating timely diagnosis and treatment.

If left untreated, gonorrhea can lead to serious health complications, including infertility, pelvic inflammatory disease, and life threatening ectopic pregnancies in women, as well as epididymitis and potential sterility in men.