Experimental Antibiotic Effective Against Gonorrhea in Early Trial

By Gene Emery

NEW YORK (Reuters Health) - The experimental anti-gonorrhea drug zoliflodacin was able to cure the infection in more than 90% of patients according to a new phase 2 test.

Researchers hope the medicine will eventually offer a new tool to fight drug-resistant strains of the disease.

Cure rates were 96% for the 113 predominantly male U.S. patients with a urogenital infection who received single-dose oral treatment with either 2 g or 3 g of zoliflodacin versus 100% among the 28 volunteers given a single 500-mg intramuscular dose of ceftriaxone.

All 15 people who had rectal infections were cured by either drug but zoliflodacin proved less adept at eliminating pharyngeal infections.

Pharyngeal cure rates were 50% for the eight people getting 2 g of zoliflodacin versus 82% for the 11 volunteers getting the 3 g dose and 100% for the four patients getting ceftriaxone therapy.

"We hoped for better activity against pharyngeal gonorrhea, but it is notoriously difficult to treat," chief author Dr. Stephanie Taylor of the Louisiana State University Health Sciences Center, in New Orleans, told Reuters Health by email. "It has been suggested that poor drug penetration into pharyngeal tissue is probably responsible for most treatment failures and not re-infection or resistant organisms."

One-third of the zoliflodacin recipients reported side effects from the treatment, most of them gastrointestinal.

Entasis Therapeutics financed the study, published in the November 8 New England Journal of Medicine. A phase 3 test of the drug is planned for next year, with results expected in 2021, a company spokeswoman told Reuters Health by email.

The results come at a time when gonorrhea infections increased 67% from 2013 through 2017 and the chance of contracting a resistant strain has also increased.

Zoliflodacin works by blocking the formation of circular DNA.

The study enrolled patients from 2014 through 2015. Four were HIV positive. Cure rates were usually assessed six days after treatment. The safety assessments were done about 31 days after therapy.

Cultures were used to determine cure rates. When the researchers looked at patients who had signs and symptoms of Neisseria gonorrhoeae, cure rates were 91% with 2 g of zoliflodacin, 94% with 3 g and 96% with ceftriaxone.

Most of the side effects were considered to be mild but 11 of the 84 adverse events were rated as moderate. Ten percent of high-dose zoliflodacin recipients had gastrointestinal disorders - all regarded as mild - that were judged to be related to the drug.

Seven percent in the high-dose group had nervous-system-related side effects considered to be attributable to the drug.

"The nervous-system-related side effects were all headache," said Dr. Taylor. Headaches were seen in "five participants (7%) in the 3 gm dose; 0% in the 2 gm dose and 3% (1 individual) in the ceftriaxone group."

There was one serious adverse event, the researchers note dryly, and that was "a nonfatal gunshot wound considered by the investigators to be unrelated to zoliflodacin."

"Although this trial did not involve a head-to-head comparison, there appear to be fewer gastrointestinal effects with zoliflodacin than with other antibiotics currently recommended for uncomplicated gonorrhea. Larger, more detailed studies are needed to define this aspect of the side-effect profile of zoliflodacin," the researchers write.

"It is more difficult to treat drug-resistant gonorrhea because over the years, N. gonorrhoeae has become resistant to every antibiotic that has been used to treat it," said Dr. Taylor. "We are currently using cephalosporins, specifically ceftriaxone, the last class of antibiotics that N. gonorrhoeae was universally sensitive to. But we are now seeing cases of resistant gonorrhea, decreased susceptibility to cephalosporins and treatment failures."

As for whether zoliflodacin will be a boon to treating resistant strains, "There is definitely hope," she said, "but one never knows until all phases of the trials are complete with results that warrant FDA approval."

Sexual health clinics in New Orleans, Indianapolis, Birmingham, Durham, and Indianapolis participated in the study.

SOURCE: https://bit.ly/2PFA52k;

N Engl J Med 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions - https://agency.reuters.com/en/copyright.html

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