EXECUTIVE SUMMARY

Early research is emerging on ETX0914, a potential candidate for treatment of gonorrhea. The drug, administered as a single-dose oral therapy, could be used as an alternative to ceftriaxone injection as a component of recommended therapy for gonorrhea, replacing the need for intramuscular injection.

  • Finding new options for treatment of gonorrhea is a high priority for public health officials. For the first time in the United States, health officials have identified a cluster of gonorrhea infections that shows both decreased susceptibility to ceftriaxone and very high-level resistance to azithromycin.
  • Although all patients were treated successfully using the recommended dual regimen, and no further cases have been identified since May 2016, both the resistance pattern and the occurrence of a cluster of cases are cause for concern.

Early research is emerging on ETX0914, a potential candidate for treatment of gonorrhea.1 The drug, administered as a single-dose oral therapy, could be used as an alternative to ceftriaxone injection as a component of recommended therapy for gonorrhea, replacing the need for intramuscular injection.

In 2015, 395,216 cases of gonorrhea were reported in the United States, for a rate of 123.9 cases per 100,000. The uptick in the gonorrhea rate during 2014-2015 was observed among both males and females; however, the increase was larger among males, rising from 119.0 to 140.9 cases per 100,000. Young adults 15-24 years of age accounted for nearly half the gonorrhea diagnoses.2

Finding new options for treatment of gonorrhea is a high priority for public health officials. For the first time in the United States, health officials have identified a cluster of gonorrhea infections that shows both decreased susceptibility to ceftriaxone and very high-level resistance to azithromycin. Although all patients were treated successfully using the recommended dual regimen, and no further cases have been identified since May 2016, both the resistance pattern and the occurrence of a cluster of cases are cause for concern.3 (For more, please see the article, “STDs at Unprecedented High in United States,” in the January 2017 issue of Contraceptive Technology Update, available at: http://bit.ly/2hrYtkh.)

N. gonorrhoeae has developed resistance to each of the antimicrobials used for treatment of gonorrhea, presenting a public health challenge. Because of declining susceptibility to cefixime, the latest CDC treatment guidelines now call for dual therapy with ceftriaxone (an injectable cephalosporin) and azithromycin as the sole CDC-recommended treatment regimen for gonorrhea.4

Potential Drug in Focus

ETX0914, which is the first of a new class of antibacterial agents targeted for the treatment of gonorrhea, operates by a novel mode of inhibition against bacterial type II topoisomerases.5 Under development by Entasis Therapeutics, it is the first of the company’s portfolio to be tested in a clinical setting, said Manos Perros, PhD, president and CEO, in a statement accompanying the Phase II results presentation.

To perform the randomized, open-label Phase II trial of ETX0914, researchers enrolled 179 patients (167 men and 12 women) with urogenital gonorrhea who were treated with ETX0914 alone (at either 2 gram or 3 gram dosage levels) or ceftriaxone alone. All patients in the 3 gram ETX0914 arm (47/47) and 98% of patients in the 2 gram arm (48/49) were cured of the infection. Scientists report the drug was well tolerated, with 21 of 179 patients reporting side effects, which were mostly mild and primarily gastrointestinal.1

The next step in research is a Phase III trial that will include a larger patient enrollment to yield information on the drug’s safety and efficacy, says Stephanie Taylor, MD, professor of medicine and microbiology at the Louisiana State University Health Sciences Center. Taylor served as the Phase II trial’s lead investigator.

Stay Vigilant

What can healthcare providers do to prevent untreatable gonorrhea from becoming a reality? The CDC encourages all providers to:

  • take a sexual history, which will help determine which sexually transmitted infections to test for, as well as at which anatomic sites;
  • adhere to CDC’s recommendations by always treating gonorrhea promptly with a combination of injectable ceftriaxone and oral azithromycin, including post-treatment testing to confirm cure when recommended.

Don’t forget to follow key CDC screening recommendations, including:

  • Screen all sexually active women younger than age 25, as well as older women with such risk factors as new or multiple sex partners, or a sex partner who has a sexually transmitted infection.
  • Screen sexually active men who have sex with men at anatomic sites of possible exposure at least annually.
  • Evaluate and treat all patients’ sex partners from the previous 60 days.
  • Obtain cultures to test for decreased susceptibility from any patients with suspected or documented gonorrhea treatment failures.
  • Report any suspected treatment failure to local or state public health officials within 24 hours. This will help ensure that any potential resistance is recognized early, according to the CDC.

REFERENCES

  1. Taylor SN, Marrazzo J, Batteiger B, et al. Phase II trial of single-dose oral ETX0914 (AZD0914) for treatment of uncomplicated urogenital gonorrhea. Presented at the 2016 STD Prevention Conference. Atlanta; September 2016.
  2. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2015. Atlanta: U.S. Department of Health and Human Services; 2016.
  3. Katz A, Komeya A, Tomas J, et al. Cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance and decreased ceftriaxone susceptibility. Presented at the 2016 National STD Prevention Conference. Atlanta; September 2016.
  4. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-3):1-137.
  5. Basarab GS, Kern GH, McNulty J, et al. Corrigendum: Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases. Sci Rep 2015;5:14157.