A billoard from the AIDS Healthcare Foundation warning of a drug-resistant gonorrhea is seen on Sunset Boulevard in Hollywood, Calif., in May, 2018.FREDERIC J. BROWN/Getty Images
Gonorrhea is on the verge of incurability, with just one antibiotic that still reliably works against the sexually transmitted infection. But on Monday, The Lancet medical journal reported successful trial results for a promising new antibiotic, making it one of the first viable gonorrhea drug candidates to come along since the 1990s.
“This is very, very exciting. I didn’t think I would see it,” says Vanessa Allen, a medical microbiologist and infectious disease physician with Sinai Health who was not involved with the study but has extensively studied drug-resistant gonorrhea.
“Without these incredible advances, there is a risk with gonorrhea that we would be unable to treat this infection in the medium term. Which is unimaginable to many of us.”
Gonorrhea is one of the most common sexually transmitted infections and can cause serious complications if left untreated, especially in women. Infection rates are rising globally and, in Canada, gonorrhea rates in 2022 were the highest recorded in 30 years, representing a three-fold jump compared to just one decade prior.
Meanwhile, the Neisseria gonorrhoeae bacterium continues its relentless evolutionary march toward superbug status, developing resistance against every drug deployed against it. The last drug standing is an injected antibiotic called ceftriaxone, but recent studies from Asia have found ceftriaxone-resistant strains in as many as 27 per cent of people tested. (In Canada, national surveillance efforts identified 13 cases of ceftriaxone-resistant gonorrhea between 2017 and 2024.)
The Lancet study, which was also presented on Monday at a major microbiology conference in Vienna, investigated an antibacterial called gepotidacin. The drug was initially developed by the pharmaceutical company GSK to treat urinary tract infections in women and girls over 12, a use that received approval from the U.S. Food and Drug Administration just last month.
The company first announced gepotidacin’s efficacy against gonorrhea at the same microbiology conference last year, but The Lancet paper is the first to publish specific details and results from the phase 3 clinical trial, which tested the drug’s efficacy and safety for treating uncomplicated urogenital gonorrhea.
In the study, more than 600 volunteers from six countries were divided into two groups to receive treatment for gonorrhea. One group took two pills of gepotidacin 10 to 12 hours apart; the other was given ceftriaxone, plus a pill called azithromycin. (Until recently, the injection-pill combo was the treatment protocol for gonorrhea but owing to rising resistance against azithromycin, many countries – including Canada – have changed their first-line therapy to ceftriaxone injections alone.)
Trial participants were given a follow-up test after four to eight days. The researchers found that 92.6 per cent of people from the gepotidacin group cleared their infections, compared with 91.2 per cent in the injection-pill group – demonstrating that the new drug is “non-inferior” for treating gonorrhea.
Both groups included people with drug-resistant strains of gonorrhea and side effects were minimal, mainly nausea and diarrhea. While the drug also worked for rectal gonorrhea, it was less effective for clearing throat infections, which are notoriously hard to treat. (The sample size for this subset was small, however, and further research is needed, the paper noted.)
These study results echo that of another recent trial co-led by The Global Antibiotic Research & Development Partnership and Innoviva Specialty Therapeutics, which showed that a single dose of a drug called zoliflodacin was also effective in treating gonorrhea. Both novel antibiotics are considered “first in class” drugs because they kill the bacteria using novel mechanisms of action – important because once a bacterium develops resistance against an antibiotic, similar drugs that rely on the same mechanism are also rendered useless.
GSK plans to file a U.S. regulatory submission in the coming months for using gepotidacin to treat urogenital uncomplicated gonorrhea and expects a regulatory decision in the second half of 2025, according to spokesperson Michelle Smolenaars Hunter.
But once gepotidacin becomes more widely used, it, too, will likely start to encounter growing resistance, experts say. “In our opinion, N. gonorrhoeae will also develop gepotidacin resistance when the selective pressure increases,” researchers Magnus Unemo and Teodora Wi wrote in a Lancet editorial, which was also published Monday.
“Gepotidacin is promising for the treatment of gonorrhea, but the challenges to retain gonorrhea as a treatable infection will continue.”
