Zoliflodacin, a novel first-in-class oral antibiotic and one of the only treatments in development to address the rapidly-growing threat of drug-resistant gonorrhea will enter pivotal trials, thanks to a new partnership between the not-for-profit Global Antibiotic Research and Development Partnership (GARDP) and Entasis Therapeutics. The announcement comes as the World Health Organization (WHO) releases alarming new data today showing that of 77 countries surveyed across the world, more than 60% report resistance to the last-resort treatment for gonorrhea.
Entasis and GARDP will co-develop the first-in-class antibiotic, zoliflodacin, in a global Phase III clinical trial to be carried out in countries including South Africa, the United States of America, and Thailand. The US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), plans to support pharmacological studies on the drug as part of the development program.
In parallel with the Phase III trial, which is sponsored by GARDP/DNDi (Drugs for Neglected Diseases initiative), GARDP will work with Entasis scientists to carry out non-clinical activities -- including microbiology surveys to ensure that the product is effective against recent and geographically diverse strains of gonorrhea. If zoliflodacin receives regulatory approval, Entasis will grant GARDP an exclusive license with sublicensing rights in most low- and middle-income countries, while retaining commercial rights in high-income markets. Both GARDP and Entasis are committed to affordable and equitable pricing in their respective territories.
"Gonorrhea has progressively developed resistance to the drugs prescribed to treat it, becoming resistant to all but last resort treatments. This partnership with Entasis aims to make sure we are ready as the last resort treatments for gonorrhea fail, so that the nightmare scenario of untreatable gonorrhea does not become a reality," said Dr Manica Balasegaram, GARDP director. "Since any new antibiotic must be effectively 'stewarded' and accessible to all who need it, we will conduct the additional studies needed not just for registration of zoliflodacin, but to have maximum public health impact -- a global approach to a global challenge."
There are about 78 million new cases of gonorrhea every year. The Neisseria gonorrhea pathogen creates a potentially serious infection in the genitals, rectum, and throat and can result in infertility, ectopic pregnancy, increased risk of HIV, and pelvic inflammatory disease amongst others. Currently, the main recommended treatment is an injection of ceftriaxone and an oral dose of azithromycin. A WHO publication released today shows resistance growing to these treatments, with the danger they could join the long list of antibiotics that have become ineffective against gonorrhea over the past decades.
"Antibiotic resistance is a serious public health issue, driving an unmet need within many communities around the world. Gonorrhea causes significant harm to patients who suffer from it, as well as accelerating the spread of other sexually transmitted infections," said Dr. Manos Perros, CEO of Entasis Therapeutics. "Zoliflodacin has the potential to stem the spread of drug-resistant gonorrhea by providing a convenient oral cure for patients and their partners. Our collaboration with GARDP demonstrates our commitment to addressing high unmet medical needs through novel antibacterials while ensuring responsible use and access to our medicines for all patients."
Entasis' zoliflodacin is the first in a new class of antibiotics and the only new clinical candidate developed specifically to treat gonorrhea, which is important for stewardship. Zoliflodacin demonstrated potent in vitro activity against Neisseria gonorrhea, including isolates resistant to fluoroquinolones and extended-spectrum cephalosporins, achieving promising efficacy after a single oral dose in a recent Phase II clinical study sponsored by NIAID. Zoliflodacin has been designated a Qualified Infectious Disease Product (QIDP) by the US Food and Drug Administration and awarded Fast Track status.
Antimicrobial resistance is recognized as a global crisis by the WHO and the G20, with calls for new mechanisms to develop new treatments. In June, the G20 held the first ever Health Ministers' meeting which called for "broadening the voluntary financial support" for initiatives, including GARDP, which "reinvigorate research and development in science and industry for antimicrobials."