A new kind of oral antibiotic to treat gonorrhea has secured Food and Drug Administration approval, the second time in two days that a new drug for the common sexually transmitted infection has come through licensure.
Neisseria gonorrhoeae, the bacterium that causes gonorrhea, has for decades been evolving to evade the antibiotics used to treat it. The current standard of care — an intramuscular injection of ceftriaxone — is the last antibiotic to reliably treat the infection, and increasingly treatment failures are being reported.
Zoliflodacin, which will be marketed under the name Nuzolvence, is the first new drug to uniquely target gonorrhea infections in decades, and the first developed as part of a public-private partnership.
The drug’s journey to market has been a long one, with multiple organizations playing a role. The license was issued to Entasis Therapeutics, which is now part of Innoviva Specialty Therapeutics, a manufacturer of drugs for infectious diseases and patients in critical care.
Innoviva and the Global Antibiotic Research and Development Partnership, GARDP, a not-for-profit organization that strives to develop treatments for drug-resistant pathogens that are accessible worldwide, brought the drug through the final stage of testing and licensure.
“This approval marks a huge turning point in the treatment of multidrug-resistant gonorrhoea, which until now has been outpacing antibiotic development,” GARDP Executive Director Manica Balasegaram said in a statement.
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“Zoliflodacin shows that a different public-private partnership approach to antibiotic development is possible — one that prioritizes global health needs, strengthens access where the burden is highest, and protects the effectiveness of new drugs for the long-term,” he said.
Innoviva will market the drug in North America and Western Europe, and GARDP will pursue efforts to have it approved in low- and middle-income countries.
Nuzolvence was approved for treatment of uncomplicated urogenital gonorrhea in individuals 12 years of age and older and weighing at least 77 pounds.
Its approval followed closely on the heels of the FDA’s granting of a supplemental license for GSK’s Blujepa — the brand name for the drug gepotidacin — as a treatment for uncomplicated urogenital gonorrhea. Blujepa had previously been approved for uncomplicated urinary tract infections.
The new treatments are sorely needed. Resistance to ceftriaxone is rising, with treatment failures reported over the last decade in Australia, France, Japan, Slovenia, Sweden, and the United Kingdom, the World Health Organization warned in October. It’s estimated that there are roughly 82 million gonorrhea infections globally each year, nearly 1.6 million in the U.S. alone.
Both new drugs have the advantage of being administered in oral form. Blujepa requires two doses, where Nuzolvence is given in a single oral suspension.
“This oral formulation has the potential to substantially improve treatment access,” authors of a Phase 3 clinical trial of Nuzolvence wrote in an article published Thursday in the journal The Lancet.
Blujepa’s supplementary approval contains some limits. It stipulates that the drug is to be used in individuals who have “limited or no alternative options” for the treatment of uncomplicated urogenital gonorrhea caused by nonresistant strains of the bacterium, either because the standard of care is contraindicated, or the patient is intolerant or unwilling to use first-line treatment. That would cover people who are allergic to the class of drugs ceftriaxone is in and people who are averse to injections.
FDA approves first new gonorrhea drug in decades
It appears from the FDA’s statement announcing the approvals that those limitations do not apply to Nuzolvence.
“The FDA’s approval of Nuzolvence marks a pivotal moment for patients and the broader healthcare community managing gonorrhea infections,” Pavel Raifeld, chief executive officer of Innoviva, said in a statement. “For the first time in decades, both patients and their healthcare providers will have a single-dose, oral treatment option for uncomplicated urogenital gonorrhea.”
Though the drugs aren’t formally approved for the treatment of rectal or oral-pharyngeal gonorrhea, in reality they will be used to treat infections in these other sites. Clinicians and the expert panels that advise them will study the drugs’ data on treating gonorrhea in the rectum or the throat and use them accordingly, said Edward Hook, a professor emeritus at the University of Alabama at Birmingham school of medicine who was senior author of the Phase 3 clinical trial testing Nuzolvence against ceftriaxone.
The study showed that the drug held promise against infections in these sites, said Alison Luckey, first author of the paper and associate director of medical sciences at GARDP. But there weren’t enough of these infections in the trial population to generate statistically significant proof.
“We believe that this is clinically meaningful data,” she told STAT. “We’re hoping this data will be referred to during treatment guideline development in the future, and certainly will provide clinicians … some data on which to make clinical decisions about their patients.”
The arrival of the drugs means the day when gonorrhea is untreatable has been pushed down the road. Given the bacterium’s facility at developing resistance — and the fact that no other new options are in late stage development at this point — no one would predict that that day will never come.
But Hook is hopeful that Nuzolvence may be a harder nut for Neisseria gonorrhoeae to crack.
The drug has a different mode of attacking gonorrhea, he noted. And to date there have been no cases of resistance to the drug observed.
“On one hand, development of resistance is an inexorable process for gonorrhea. It’s just always going to happen. On the other hand, I think this drug is relatively resistant to development of resistance. And that’s a good thing,” Hook said.
