Uncomplicated Super-Gonorrhea Treated with First-in-Class Oral Antibiotic
The first study to address a World Health Organization (WHO) priority pathogen, gonorrhea, recently found positive preliminary findings that offer hope for patients, particularly in the face of rising antibiotic resistance to current regimens.
If approved, zoliflodacin will be the first new antibiotic for treating 'super-gonorrhea' in decades.
The Global Antibiotic Research & Development Partnership (GARDP), in collaboration with Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc., announced on November 1, 2023, that zoliflodacin, a first-in-class antibiotic, met its primary endpoint in an unprecedented global pivotal phase 3 clinical trial.
Study investigators found that oral zoliflodacin demonstrated statistical noninferiority in microbiological cure at the urogenital site compared to treatment with intramuscular ceftriaxone and oral azithromycin, a current global standard of care regimen.
In this late-stage study, zoliflodacin was found to be generally well tolerated, and no serious adverse events or deaths were recorded.
The phase 3 trial enrolled a total of 930 patients with uncomplicated gonorrhea, including women, adolescents, and people living with HIV, making it the largest clinical trial ever conducted for a new treatment against gonorrhea infection, with 16 trial sites in regions with a high prevalence of gonorrhea across five countries, including Belgium, the Netherlands, South Africa, Thailand, and the U.S.
Dr. Manica Balasegaram, Executive Director of GARDP, commented in a related press release, "Despite the extremely high public health value, there has been a lack of investment to develop new drugs for gonorrhea."
"This zoliflodacin program demonstrates that it is possible to develop antibiotic treatments targeting multidrug-resistant bacteria that pose the greatest public health threat and which may not otherwise get developed."
With more than 82 million new gonorrhea infections occurring globally each year, gonorrhea is the third most common sexually transmitted infection (STI), affecting both men and women.
If left untreated, gonorrhea can also cause infertility in women, life-threatening ectopic pregnancies, and pelvic inflammatory disease.
The bacterium Neisseria gonorrhoeae has gradually developed resistance to many classes of antibiotics used to treat these infections. As a result, ceftriaxone, given as a single intramuscular injection, has become the last available recommended treatment for gonorrhea globally.
The clinical trial compared a single oral 3g dose of zoliflodacin to a globally recognized standard of care regimen (500mg ceftriaxone plus 1g oral azithromycin) for the treatment of uncomplicated gonorrhea.
Zoliflodacin met the prespecified statistical test for noninferiority compared to ceftriaxone and oral azithromycin (5.31% (95%CI 1.38, 8.65%)).
Noninferiority of zoliflodacin was demonstrated within the prespecified margin of 12% and, furthermore, within the margin of 10% as specified in U.S. Food and Drug Administration guidance.
GARDP has the right to register and commercialize the product in more than three-quarters of the world's countries. Limited, an affiliate of Innoviva Specialty Therapeutics, retains commercial rights for zoliflodacin in the major markets in North America, Europe, Asia-Pacific, and Latin America.
The governments of Germany, the U.K., Japan, the Netherlands, Switzerland, and others funded this GARDP-led trial.
GARDP is a Swiss non-profit organization that develops new treatments for drug-resistant infections that pose the greatest threat to health. It was created by the World Health Organization and the Drugs for Neglected Diseases initiative in 2016 and legally founded in 2018.
As of November 2023, gonorrhea, like herpes, syphilis, and other STIs, does not have U.S. FDA-approved vaccines available.
However, a Research Letter published by the JAMA Network Infectious Diseases on August 31, 2023, concluded that an outer membrane vesicles-based meningococcal group B vaccine was 47% (95% CI, 13%-68%) effective in preventing gonorrhea among recipients aged 18 to 29.