New Antibiotic Zoliflodacin Offers Hope Against Multidrug-Resistant Gonorrhea

Neisseria gonorrhoeae

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This article first appeared in our sister brand, Contagion®Live.

The incidence of STIs has been increasing in the US over the past few years, with a disproportionate impact among MSM and transgender women. According to the CDC, an estimated 2.5 million cases of syphilis, gonorrhea, and chlamydia occurred in 2021, which is up from 2.4 million cases in 2020.¹

Within STIs, there is a newer virulent multidrug-resistant strain of gonorrhea. Specifically, the penA 60.001 allele in N gonorrhoeae, a genetic variation helps contribute to antibiotic resistance. The penA 60.001 allele alters the bacterial response to cephalosporins.² This strain of Neisseria gonorrhoeae, ranked among the highest-tier “urgent threats” among the 18 bacteria and fungi on the CDC's 2019 antibiotic resistance threats report.

Although the multidrug-resistant gonorrhea strain has been seen mostly outside the US, last year 2 cases of this pathogen were confirmed in the US and identified by the Massachusetts Department of Public Health. Massachusetts officials reported that clinicians were able to treat the patients successfully with ceftriaxone. However, this strain of the sexually transmitted infection had reduced susceptibility to 5 antibiotic classes—including cephalosporins, the group of last-resort drugs that includes ceftriaxone.³

As there has been an increase in the STI and the emergence of a multidrug-resistant threat, a need for newer therapies has arisen.

Zoliflodacin a first-in-class oral, single-dose antibiotic for the treatment of uncomplicated gonorrhea is in late stage clinical trials, and has demonstrated efficacy and safety. This phase 3 trial was a global, randomized, controlled study that evaluated the efficacy and safety of zoliflodacin.

The topline data from this trial was previously disclosed at the European Society of Clinical Microbiology and Infectious Disease (ESCMID) 2023, which showed that zoliflodacin was noninferior to a combination of ceftriaxone and azithromycin (5.31%, 95% confidence interval: 1.38-8.65) with urogenital microbiological cure rates of 90.9% (88.1-93.3) and 96.2% (92.9-98.3), respectively, for the microbiological intent-to-treat population. Zoliflodacin had a favorable safety profile with comparable overall number of adverse events between the treatment arms.⁴

At this week’s ID Week 2024, Innoviva Specialty Therapeutics CMO David Altarac, MD, will be presenting data on zoliflodacin. “The data that we are here to present is for the treatment of gonorrhea, including resistant strains of gonorrhea,” he said in an interview with Contagion.

Altarac says the company is looking at 1 main indication for the therapy. “We are focused on developing the drug for uncomplicated gonorrhea. We believe that, as we've done with other products, a focus on targeted development will advance the efforts towards developing products that have specific focus will be used responsibly, and will hopefully increase the longevity of that product," he said.

With the phase 3 results, the company is planning to file for FDA approval. “We are targeting a new drug application in the United States for the first quarter of next year. Zoliflodacin has been reviewed by the FDA and given both qualified infectious disease product and fast track designation; therefore, if our new drug application is accepted, we would aim for a priority review,” Altarac said.

References

1. Sexually Transmitted Infections (STIs). CDC. Last reviewed January 30, 2024. Accessed October 16, 2024. https://www.cdc.gov/std/statistics/2022/default.htm
2. Abene S. A Growing Concern About Gonorrhea's Resistance to Antibiotics. Contagion. January 26, 2024. Accessed October 16, 2024.
https://www.contagionlive.com/view/a-growing-concern-about-gonorrhea-s-resistance-to-antibiotics
3. Landhuis EW. Multidrug-Resistant “Super Gonorrhea” Rallies Multipronged Effort. JAMA. 2024;331(20):1695–1697. doi:10.1001/jama.2023.15355
4. Innoviva Specialty Therapeutics Presents Findings from Subgroup Analyses of zoliflodacin in uncomplicated gonorrhea at the 2024 Sexually Transmitted Infections Conference. Innoviva press release. September 19, 2024. Accessed October 16, 2024.
https://innovivaspecialtytherapeutics.com/innoviva-specialty-therapeutics-presents-findings-from-subgroup-analyses-of-zoliflodacin-in-uncomplicated-gonorrhea-at-the-2024-sexually-transmitted-infections-conference/