A new antibiotic has proven as effective as the last remaining recommended treatment for gonorrhea, helping to assuage mounting fears among public health experts about the emergence of drug-resistant strains of the sexually transmitted infection.
Gonorrhea is the second most common STI in the U.S. and has developed resistance to all antibiotics used to treat it, except for the recommended combined therapy of an injection of the antibiotic ceftriaxone with one dose of azithromycin pills. In recent years, ominous reports have suggested that this antibiotic arsenal might not maintain its robust effectiveness against the fast-evolving pathogen for much longer.
On Wednesday, results from a late-stage clinical trial of a new antibiotic called zoliflodacin showed the drug cured so-called uncomplicated gonorrhea infections as effectively as ceftriaxone and azithromycin. The drug was developed by the Global Antibiotic Research & Development Partnership, a Swiss nonprofit, and the U.S.-based Innoviva Specialty Therapeutics.
“Zoliflodacin gives us a new tool in the treatment of gonorrhea, and if used wisely, a barrier against the further spread of resistant infections,” said Dr. Jeffrey Klausner, an infectious disease expert at the Keck School of Medicine of USC, who was not involved in the trial.
The antibiotic, which would be the first new gonorrhea treatment approved in decades, could make it to market by 2025.
The World Health Organization estimates that globally there are more than 82 million new gonorrhea cases every year. In the U.S., in the wake of decades of cuts to state and local public health departments, STIs have soared to record heights. In 2021, there were 710,151 diagnosed cases of gonorrhea, a 28% increase since 2017, according to the Centers for Disease Control and Prevention.
Gonorrhea spreads through sexual contact and can separately infect the genitals, rectum and throat.
The STI is especially common among adolescents and young adults and occurs disproportionately among gay and bisexual men, the CDC reports. Left untreated, gonorrhea poses a risk of infertility and can prove especially damaging to women, leading to pelvic inflammatory disease and ectopic pregnancy. The infection can also raise the risk of HIV transmission.
In recent years, global health authorities have issued increasingly urgent warnings that gonorrhea has been acquiring resistance to ceftriaxone and azithromycin, with cases of highly drug-resistant gonorrhea reported in multiple nations.
In January, the Massachusetts Department of Public Health reported the first two U.S. cases of gonorrhea that had resistance or reduced response to five classes of antibiotics. Ceftriaxone did cure those cases, but public health officials said they served as a harbinger for the emergence of strains that could evade the antibiotic.
Without a new antibiotic weapon, curing highly drug-resistant strains of gonorrhea could require intensive treatment with multiple antibiotics, according to Dr. Jeanne Marrazzo, director of the National Institute of Allergy and Infectious Diseases. This so-called kitchen-sink approach, she said, would strain medical resources and raise the risk of driving the emergence of further microbial drug resistance to those other antibiotics.
The ultimate fear is that eventually, gonorrhea could prove wholly untreatable, in at least some people.
According to an Innoviva representative, the company aims to file for approval of the antibiotic with the Food and Drug Administration “as quickly as practicably possible.” Innoviva expects an expedited review, meaning the FDA would take about six months to issue a decision.
Zoliflodacin belongs to a new class of antibiotics, and attacks gonorrhea in a novel way. In previous laboratory studies, zoliflodacin proved effective at neutralizing gonorrhea strains that were highly resistant to ceftriaxone and azithromycin and strains that had resistance to other antibiotics as well.
A downside of zoliflodacin is that a previous, phase two clinical trial published in 2018 found that it was not as efficacious at treating gonorrhea infections in the throat as in the genital or rectal areas. However, Marrazzo, who was a co-author on that study, said that this disparity is common among gonorrhea treatments.
“Gonorrhea in the throat is probably going to be a major Achilles heel in our battle to control gonorrhea going forward,” Marrazzo said.
But according to Dr. Margaret Koziel, chief medical officer of Innoviva, the new zoliflodacin trial showed “encouraging” results in the small number of participants with rectal or throat infections.
The company “will certainly engage the FDA about whether the label indication might be for urogenital disease or for all uncomplicated gonorrhea,” Koziel said.
According to Dr. Manica Balasegaram, executive director of Global Antibiotic Research & Development Partnership — Innoviva’s partner in the trial — zoliflodacin holds promise in retaining potency against gonorrhea for a longer period than previous treatments for the infection, because it was developed solely as a treatment for that STI. Ceftriaxone and azithromycin are each used to combat numerous other infections; and the more they are used, the more opportunity gonorrhea has to develop resistance to them.
“This new drug is also given orally instead of an intramuscular injection with ceftriaxone; this is an advantage,” said Dr. Jean-Michel Molina, who studies STI prevention at the University of Paris and was not involved in the clinical trial.
Molina is the head of one of the multiple clinical trials currently running of a meningitis B vaccine as prevention for gonorrhea. He said he expects to present final results of his trial at a scientific meeting in 2024.
The new zoliflodacin study enrolled 930 men, women and adolescents, including people with HIV, with uncomplicated gonorrhea at 16 trial sites in five nations, including Belgium, the Netherlands, South Africa, Thailand and the U.S. Participants were randomized to receive a single oral dose of zoliflodacin or a ceftriaxone injection plus oral azithromycin.
The WHO has called the emergence of drug-resistant pathogens one of the top 10 global public health threats facing humanity and has identified gonorrhea in particular as a priority pathogen.
The zoliflodacin trial is the first to address such a priority pathogen that was marshalled by a nonprofit organization. Established in 2016 by the WHO to help shepherd new antibiotics to market, efforts by the Global Antibiotic Research & Development Partnership’ represent a promising new front in the vital effort to spur research and development of new antibiotics. Offering only thin profit margins, antibiotics do not tend to attract investment by pharmaceutical companies.
“Treating gonorrhea, it’s not going to be your next Ozempic,” said Marrazzo.