Gonorrhea, a sexually transmitted infection caused by Neisseria gonorrhoeae, is among the most pressing health threats according to the World Health Organization. In 2024, its resistance to standard antibiotics such as ceftriaxone has experienced a worrying increase, with rates increasing sixfold in several countries. Long deprived of new therapeutic solutions, the treatment of this infection found itself at an impasse. Two new oral antibiotics have just been approved by the United States Medicines Agency (FDA), marking a critical step in the fight against resistant strains.
Zoliflodacin, developed by GARDP (Global Antibiotic Research and Development Partnership) in partnership with Innoviva, and gepotidacin, designed by GSK, have both demonstrated their effectiveness in clinical trials published in The Lancet. These trials were carried out by researchers from several institutions, including Imperial College London and Örebro University.
An infection on the rise and increasingly difficult to treat
Gonorrhea, caused by bacteria Neisseria gonorrhoeaeis experiencing a global outbreak. In 2024, it is estimated that there will be more than 82 million new infections annually. However, this figure masks a more worrying reality: the rapid rise in bacterial resistance to standard treatments. The World Health Organization (WHO) has classified it among the “
priority pathogens » due to this development.
Until recently, the standard treatment was an injection of ceftriaxone, often combined with an oral antibiotic, azithromycin. But this scheme is proving less and less effective. A WHO surveillance program revealed a spectacular increase in resistance to these two antibiotics between 2022 and 2024: from 0.8% to 5% for ceftriaxone, and from 1.7% to 11% for cefixime. This means that in some countries, one in ten patients may receive ineffective treatment.
The most affected regions are Africa and the Asia-Pacific region, but Europe is not spared. In the United Kingdom, cases reached record levels in 2023, and rates have tripled in Europe since 2014. These figures reflect a double challenge: the increase in the number of infections and the loss of effectiveness of available drugs.
The clinical consequences appear to be serious. In women, gonorrhea can cause pelvic inflammatory disease leading to infertility or ectopic pregnancy. In men, it can also lead to infertility. In rare cases, the bacteria spreads into the blood or joints, causing serious forms. Faced with this threat, health authorities are alarmed by the real risk of gonorrhea becoming incurable.
Zoliflodacin, a targeted response resulting from an unprecedented collaboration
Zoliflodacin, registered under the trade name Nuzolvence, is the first oral treatment from a new class of antibiotics called spiropyrimidinetriones. It was developed specifically to target Neisseria gonorrhoeaeand constitutes a strategic breakthrough in antibiotic development. This drug was developed by GARDP (Global Antibiotic Research and Development Partnership), in partnership with Innoviva Specialty Therapeutics, as part of a unique model of non-profit collaboration.
This approach must produce effective treatments while limiting the risks of overuse, a key factor in the emergence of resistance. As Dr Manica Balasegaram, Executive Director of GARDP, points out at Guardian, “ Zoliflodacin is only intended to treat gonorrhea. This decreases the likelihood of cross-resistance with other infections.”
The drug was evaluated in a phase 3 clinical trial, including 930 participants aged 12 and over, conducted in five countries: Belgium, the Netherlands, South Africa, Thailand and the United States. The results showed that zoliflodacin cured 90.9% of urogenital infections. This rate remains comparable to that of standard treatment, while presenting a favorable safety profile. Side effects were limited to headache or transient blood count abnormalities.
Administration is done orally in a single dose, in the form of soluble granules. This facilitates its use outside medical structures. This simplicity is crucial in low-resource contexts. Additionally, GARDP holds the rights to distribute the drug in more than 160 low- and middle-income countries. A point reinforcing equitable access to this treatment.
Gepotidacin a validated alternative treatment for complex cases
Gepotidacin, marketed under the name Blujepa, is another oral antibiotic recently approved by the Food and Drug Administration (FDA). Unlike zoliflodacin, which is dedicated exclusively to gonorrhea, gepotidacin is a broader spectrum treatment. It is already approved in the United States for uncomplicated urinary tract infections in women.
Developed by the GSK laboratory, this medication is intended for patients aged 12 and over, weighing at least 45 kilos, in cases where traditional treatments are ineffective or contraindicated. It acts by a different mechanism than existing antibiotics, which makes it potentially effective against resistant strains.
The results of an international clinical trial conducted between 2019 and 2023 in six countries (United States, United Kingdom, Germany, Spain, Mexico and Australia) were published in April in
The Lancet. Of the 600 participants, treatment with gepotidacin (two oral doses 10-12 hours apart) cured 92.6% of cases. A rate equivalent to that of standard treatment combining ceftriaxone injection and azithromycin.
The side effects observed mainly concerned digestive disorders (nausea, diarrhea), classified as mild or moderate. No serious adverse effects have been reported. The dosage remains simple but requires taking it in two stages, unlike zoliflodacin.
GSK's commercial strategy calls for a retail price of approximately $1,900 for a bottle of 20 tablets, with a standard course of 8 tablets. However, patient costs will vary between health systems and reimbursements. This pricing already raises questions about overall accessibility. Particularly in countries with limited resources, where gonorrhea is progressing rapidly.
Towards a new global management of bacterial resistance
The arrival of these two new treatments opens a strategic window to strengthen the global fight against antimicrobial resistance. However, their long-term effectiveness will depend on their rational use, epidemiological surveillance, and integration into public health policies.
According to Dr. David Altarac, medical director at Innoviva, cited by CNN“ the objective is also to preserve these new molecules by avoiding their overprescription, to delay the emergence of resistance as much as possible. “. The WHO shares this concern. It recommends targeted use, based on local resistance data.
From this perspective, the development of zoliflodacin for exclusive use against gonorrhea represents a “stewardship” approach (reasoned management of antibiotics). This strategic choice makes it possible to limit the selective pressure exerted on the bacterial flora in general. This therefore slows down the appearance of new resistant mutations.
At the same time, vaccine research continues. Recent studies, notably in the United Kingdom, are exploring the potential of the meningococcal B vaccine to reduce the risk of gonorrhea, as the two bacteria are genetically close. This combination of prevention and treatment could strengthen the impact of current measures.
Finally, equitable access to treatments remains a major challenge. GARDP, holder of the distribution rights for zoliflodacin in low- and middle-income countries, is committed to guaranteeing differentiated pricing adapted to local contexts.
But Professor Magnus Unemo, from Örebro University and WHO advisor, is warning. “ These treatments are progress, but they are not enough. The resistance will continue to evolve. You must maintain an active pipeline of solutions “. Scientific vigilance and international coordination therefore remain essential.
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