• A phase 3 study of oral zoliflodacin met the primary endpoint when compared against the combination of injectable ceftriaxone and oral azithromycin, a current international standard of care.
• Positive top-line study results are a significant milestone in the development of a first-in-class antibiotic against drug resistant Neisseria gonorrhoeae, a high priority pathogen.
• Groundbreaking antibiotic research & development partnership model paves the way for development of other antibiotics to address impact of antimicrobial resistance (AMR).

Geneva (Switzerland) and Waltham, MA (USA), 1 November 2023 – The Global Antibiotic Research & Development Partnership (GARDP) in collaboration with Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc. (Nasdaq: INVA), announced today that zoliflodacin, a first-in-class antibiotic, met its primary endpoint in an unprecedented global pivotal phase 3 clinical trial. Study investigators found that oral zoliflodacin demonstrated statistical non-inferiority of microbiological cure at the urogenital site when compared to treatment with intramuscular injection of ceftriaxone and oral azithromycin, a current global standard of care regimen. In the study, zoliflodacin was found to be generally well tolerated and there were no serious adverse events or deaths recorded in the trial.

This is the first study to address a World Health Organization priority pathogen that has been sponsored and led by a non-profit organization. These positive preliminary findings offer hope for patients with this condition, particularly in the face of rising antibiotic resistance to current regimens. It also paves the way for a new research and development model in the global fight against antimicrobial resistance (AMR). If approved, zoliflodacin will be the first new antibiotic for treating gonorrhea in over 30 years.  

“This is a significant step forward in the treatment of gonorrhea, and also shows that GARDP’s public-private partnership model can play a crucial role in helping to fix the public health failure at the heart of the global AMR crisis,” said Dr. Manica Balasegaram, Executive Director of GARDP. “Despite the extremely high public health value, there has been a lack of investment to develop new drugs for gonorrhea. This zoliflodacin program demonstrates that it is possible to develop antibiotic treatments targeting multidrug-resistant bacteria that pose the greatest public health threat, and which may not otherwise get developed.”

With more than 82 million new gonorrhea infections occurring globally each year, gonorrhea is the third most common sexually transmitted infection, affecting both men and women in ways that can result in serious and permanent health consequences. The bacterium Neisseria gonorrhoeae has gradually developed resistance to many classes of antibiotics used to treat these infections and as a result, ceftriaxone, given as a single intramuscular injection, has become the last available recommended treatment for gonorrhea globally.

“The outcome of this study is a game changer for sexual health,” said Edward W. Hook III MD, Protocol Chair for the study and Emeritus Professor of Medicine at the University of Alabama, in Birmingham. “In addition to the benefits for patients with infections with resistant strains of Neisseria gonorrhoeae, the potential lack of cross-resistance with other antibiotics and the oral route of administration will simplify gonorrhea therapy for clinicians worldwide.”

Recent reports (The Lancet Infectious Diseases) of emergent ceftriaxone-resistant infections have heightened the urgency for new antibiotics. Effective treatment options are essential to reducing the burden of disease for individuals, and to preventing the spread of highly drug-resistant gonorrhea globally. If left untreated, gonorrhea can also cause infertility in women, life-threatening ectopic pregnancies, and pelvic inflammatory disease.²

“The success of this study could have a profound effect on how physicians approach gonorrhea infections, as an oral alternative to an injection could improve patient access and compliance, as well as help reduce the increasing spread of antibiotic resistant strains of the disease,” said Pavel Raifeld, Chief Executive Officer, Innoviva, Inc. “Such a positive outcome represents an important milestone for Innoviva Specialty Therapeutics and reinforces our position as a premier infectious disease and critical care company, especially when coupled with the recent launch of XACDURO^Ò.”

Zoliflodacin has a unique mechanism of action in the way that it inhibits a crucial bacterial enzyme called type II topoisomerase, which is essential for bacterial function and reproduction. Previous studies have shown that it is active against multi-drug resistant strains of Neisseria gonorrhoeae, including those resistant to ceftriaxone, and azithromycin, with no cross-resistance with other antibiotics. Now, the positive results of this landmark phase 3 trial confirm that zoliflodacin has the potential to tackle the most difficult-to-treat gonorrhea infections.

The Phase 3 trial enrolled a total of 958 patients with uncomplicated gonorrhea, including women, adolescents and people living with HIV, making it the largest clinical trial ever conducted for a new treatment against gonorrhea infection, with 16 trial sites in regions with a high prevalence of gonorrhea across five countries, including Belgium, the Netherlands, South Africa, Thailand, and the U.S. The trial compared a single oral 3g dose of zoliflodacin to a globally recognized standard of care regimen (500mg ceftriaxone IM plus 1g oral azithromycin) for the treatment of uncomplicated gonorrhea. The clinical trial has also helped to boost skills in Thailand.

“Thailand is an emerging leader for clinical trials thanks to national policies supporting research activities, its universal healthcare system, highly skilled research workforce and access to world-class medical equipment and facilities. Data shows a high prevalence of gonorrhoea in Thailand, and this trial allowed us to test safety and effectiveness of a new antibiotic, zoliflodacin, for an infection that has progressively developed resistance to available treatments.”  said Dr Rossaphorn Kittiyaowamarn, Chief of Bangrak STIs Center

Zoliflodacin met the prespecified statistical test for non-inferiority when compared to ceftriaxone and oral azithromycin (5.31% (95%CI 1.38, 8.65%). Non inferiority of zoliflodacin was demonstrated within the pre-specified margin of 12% and, furthermore, within the margin of 10% as specified in FDA guidance.

GARDP has the right to register and commercialize the product in more than three-quarters of the world’s countries, including all low-income countries, most middle-income countries, and several high-income countries. GARDP is committed to work with its partners and local health authorities in markets where zoliflodacin receives regulatory approval, to help remove access barriers to ensure treatment is available to address unmet medical needs while ensuring appropriate and sustainable use. Entasis Therapeutics Limited, an affiliate of Innoviva Specialty Therapeutics, retains the commercial rights for zoliflodacin in the major markets in North America, Europe, Asia-Pacific, and Latin America.

This GARDP-led trial was funded with support from the governments of Germany (BMBF and BMG), UK (DHSC, GAMRIF and DFID), Japan (MHLW), the Netherlands (Ministries of VWS and BZ), Switzerland (FOPH), The Grand Duchy of Luxembourg, as well as the Canton of Geneva, South African MRC, and the Leo Model Foundation. This builds on the critical phase 2 clinical trial sponsored by the U.S. National Institute of Allergy and Infectious Diseaseas (NIAID).

About GARDP

The Global Antibiotic Research and Development Partnership is a Swiss, not-for-profit organization developing new treatments for drug-resistant infections that pose the greatest threat to health. GARDP was created in 2016 by the World Health Organization (WHO) and the Drugs for Neglected Diseases initiative (DNDi) and legally founded in 2018 to ensure that everyone who needs antibiotics receives effective and affordable treatment, no matter where they live. It aims to develop new treatments to fight drug-resistant infections, with a focus on sexually transmitted infections, sepsis in newborns, and infections in hospitalized adults and children. GARDP is funded by the governments of Australia, Germany, Japan, Luxembourg, Monaco, Netherlands, South Africa, Switzerland, United Kingdom, the Canton of Geneva, as well as Médecins Sans Frontières and private foundations. GARDP is registered under the legal name GARDP Foundation. www.gardp.org

เกี่ยวกับ SICRES

The Siriraj Institute of Clinical Research (SICRES) is an academic clinical research institute that operates under the Faculty of Medicine Siriraj Hospital, Mahidol University. Our mission is to conduct and support clinical research trials to transform patient care, improve human health, and better the community. We conduct cost-effective clinical research at international standards and provide full-service clinical trial design and management. Our vision is to become the most trusted academic clinical research organization in Southeast Asia. www.sicres.org/