Entasis Therapeutics (NASDAQ: ETTX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel antibacterial products, announced that The New England journal of Medicine (NEJM) published results from a Phase 2 clinical trial evaluating the safety and efficacy of zoliflodacin in patients with uncomplicated gonorrhea. Zoliflodacin represents a new type of oral antibiotic that inhibits DNA synthesis in a manner different from currently approved classes of antibiotic drugs. The clinical trial was sponsored by The National Institute of Allergy and Infectious Disease (NIAID), part of the U.S. National Institutes of Health (NIH).
Gonorrhea is a common sexually transmitted disease (STD) that affects both men and women, particularly young people ages 15 to 24 years. Gonorrhea is the second most commonly reported notifiable disease in the United States. In 2017, more than 550,000 cases of gonorrhea were reported in the United States. If untreated, gonorrhea infection can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and an increased risk of HIV infection. Pregnant women can pass the infection to their babies, who can become blind or develop life-threatening infections as a result.
Gonorrhea is caused by the bacterium Neisseria gonorrhoeae, which has progressively developed resistance to each of the antimicrobials used to treat it. As a result, in 2015, the U.S. Centers for Disease Control and Prevention revised gonorrhea treatment guidelines to recommend dual therapy with injectable ceftriaxone and oral azithromycin to reduce the emergence of resistance to ceftriaxone.
“The rate of reported gonorrhea cases in the United States has increased 75 percent since the historic low in 2009, and antibiotic resistance has considerably reduced the number of treatment options for this disease,” said NIAID Director Anthony S. Fauci, M.D. “These research findings published today suggest that zoliflodacin has the potential to be a useful and easy-to-administer oral antibiotic for treating gonorrhea.”
The study took place from November 2014 through December 2015 and was a multi-center, randomized, open-label study that enrolled 179 participants (167 men, and 12 non-pregnant women) between the ages of 18 to 55 with either symptoms of uncomplicated urogenital gonorrhea, untreated urogenital gonorrhea or sexual contact with someone with gonorrhea within 14 days before enrollment. Participants were randomly selected to receive either a single 2- or 3-gram dose of oral zoliflodacin or a 500 milligram (mg) dose of injectable ceftriaxone. Among the 117 per-protocol participants who were evaluated six days after treatment, 98 percent (48 of 49 participants) of those who received the 2-gram zoliflodacin dose, 100 percent (47 of 47 participants) of those who received the 3-gram dose, and all (21 of 21) of the participants in the ceftriaxone group were considered cured of their urogenital gonorrhea based on culture results.
Zoliflodacin cured all rectal gonorrheal infections (5 of 5 participants who received the 2-gram dose; 7 of 7 participants who received the 3-gram dose) as did ceftriaxone (3 of 3 participants). In treating patients with gonorrhea infections of the throat (pharyngeal), 50 percent of volunteers who received the 2-gram dose (4 of 8 participants) and 82 percent of those who received the 3-gram dose (9 of 11 participants) were cured. All of the participants (4 of 4) in the ceftriaxone group achieved a cure. Zoliflodacin was generally well-tolerated with transient gastrointestinal upset the most commonly reported adverse effect. Microbiological evaluation of post-treatment clinical isolates did not show any resistance to zoliflodacin.
“We are grateful for the work done by the NIAID and pleased to have data on zoliflodacin published in the New England Journal of Medicine,” stated Manos Perros, President and Chief Executive Officer of Entasis Therapeutics. “The results highlighted in the NEJM’s publication provide support for the therapeutic potential of zoliflodacin in gonococcal infections and we look forward to advancing our Phase 3 clinical trial.”
Zoliflodacin has received Fast Track designation and qualified infectious disease product (QIDP) designation by the U.S. Food and Drug Administration (FDA) for development solely as oral treatment for gonococcal infections. Entasis, in partnership with GARDP, will begin Phase 3 testing of zoliflodacin in the Netherlands, South Africa, Thailand and the United States next year.
Zoliflodacin is a novel oral antibiotic for the treatment of uncomplicated gonorrhea and the first of a novel class of molecules to be developed for this indication. Uncomplicated gonorrhea is becoming increasingly difficult to treat as the Neisseria gonorrhoeae bacterium has developed resistance to successive classes of antibiotics. There are currently few oral treatment options, and the Centers for Disease Control and Prevention (CDC) has designated N. gonorrhoeae an urgent public health threat that requires aggressive action. N. gonorrhoeae has developed resistance to all classes of antimicrobials previously recommended for treatment of uncomplicated gonorrhea. As a result, the CDC treatment guidelines require dual therapy with injectable ceftriaxone and oral azithromycin.
Uncomplicated gonorrhea infections carry high morbidity, enhance transmission of other sexually transmitted diseases and are highly stigmatized. Published studies have demonstrated the potent in vitro activity of zoliflodacin against N. gonorrhoeae, including isolates resistant to fluoroquinolones and extended spectrum cephalosporins. Zoliflodacin received Fast Track designation and qualified infectious disease product (QIDP) designation by the U.S. Food and Drug Administration (FDA).