Innoviva Specialty Therapeutics, a subsidiary of Innoviva, today announced that the U.S. Food and Drug Administration (FDA) has approved NUZOLVENCE (zoliflodacin) for oral suspension, a first-in-class, single-dose oral antibiotic for the treatment of uncomplicated urogenital gonorrhea in adults and adolescents aged 12 years and older who weigh at least 35 kilograms.
The FDA approval represents a major milestone in the management of gonorrhea, marking one of the first new treatment options approved in nearly two decades for this widespread sexually transmitted infection (STI). The decision was supported by results from the largest Phase 3 clinical trial ever conducted for a new therapy targeting Neisseria gonorrhoeae, carried out across regions with a high burden of disease in five countries.
Addressing a Longstanding Public Health Challenge
Gonorrhea remains one of the most common bacterial STIs globally, with an estimated more than 82 million new infections each year worldwide. In the United States, it is the second most frequently reported bacterial STI, with the Centers for Disease Control and Prevention (CDC) estimating over 543,000 reported cases annually, alongside more than one million new infections each year. These figures underscore the persistent and significant public health challenge posed by gonorrhea.
While gonorrhea is often treatable, untreated or inadequately managed infections can result in serious and sometimes irreversible complications. These include pelvic inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain, and an increased risk of HIV transmission. Young adults—particularly sexually active men between the ages of 20 and 24—experience the highest infection rates, though anyone engaging in unprotected sexual activity is at risk.
A Breakthrough in Gonorrhea Treatment
NUZOLVENCE is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor, a novel mechanism of action that distinguishes it from previously approved antibiotics. Importantly, NUZOLVENCE is administered as a single oral dose, offering a non-injectable alternative to existing treatments.
Currently, the standard first-line therapy for uncomplicated urogenital gonorrhea relies on injectable ceftriaxone, a cephalosporin antibiotic. However, the bacterium Neisseria gonorrhoeae has demonstrated a troubling ability to develop resistance to multiple antibiotic classes over time, including cephalosporins. As resistance continues to rise globally, treatment options have become increasingly limited.
NUZOLVENCE’s approval introduces a much-needed alternative, particularly for patients who are unable to receive injectable therapy or who have allergies to beta-lactam antibiotics such as penicillin.
Clinical Evidence Supporting Approval
The FDA’s decision was based on robust data generated from a large, multicenter Phase 3 clinical trial sponsored and led by the Global Antibiotic Research and Development Partnership (GARDP), a private, not-for-profit organization focused on developing treatments for drug-resistant infections.
The pivotal study demonstrated that NUZOLVENCE was non-inferior to the current standard injectable therapy in treating uncomplicated urogenital gonorrhea. Notably, the drug was effective across a broad range of patient populations and maintained efficacy against infections caused by drug-resistant strains of Neisseria gonorrhoeae.
The trial’s scale and geographic diversity were designed to reflect real-world disease prevalence and resistance patterns, strengthening confidence in the generalizability of the findings.
Expert Perspectives
The FDA approval of NUZOLVENCE represents a transformative moment in the treatment of gonorrhea said David Altarac, M.D., Chief Medical Officer of Innoviva Specialty Therapeutics. “For the first time in decades, healthcare providers and patients will have access to a single-dose, oral treatment option for uncomplicated urogenital gonorrhea. This approval reflects our commitment to advancing innovation in infectious diseases and addressing the growing threat of antimicrobial resistance
Dr. Altarac also highlighted the importance of collaboration in achieving this milestone. “The development of NUZOLVENCE showcases the power of global partnerships, particularly our collaboration with GARDP and the broader scientific community.”
Edward W. Hook III, M.D., Professor Emeritus of Medicine at the University of Alabama at Birmingham and lead investigator of the Phase 3 trial, emphasized the significance of the new therapy. “The absence of new gonorrhea treatments for decades, combined with escalating antibiotic resistance, has created a serious challenge in managing this infection. In the pivotal Phase 3 study, NUZOLVENCE demonstrated strong efficacy, including against resistant strains, while offering the convenience of a single oral dose.”
Dr. Hook added that NUZOLVENCE addresses critical unmet needs. “A new antibiotic that does not require injection and can be used in patients allergic to penicillin or related drugs fills two major gaps in current gonorrhea treatment.”
Combating Antimicrobial Resistance
The approval of NUZOLVENCE comes at a time when antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the top 10 global health threats. Neisseria gonorrhoeae is listed as a high-priority pathogen due to its increasing resistance to nearly all antibiotics historically used to treat it.
By introducing a novel mechanism of action, NUZOLVENCE may help reduce reliance on existing antibiotics and slow the spread of resistant strains when used appropriately.
Intended Use and Stewardship Considerations
NUZOLVENCE is indicated for the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae in adults and pediatric patients aged 12 years and older weighing at least 35 kg.
To preserve its effectiveness and reduce the risk of resistance development, NUZOLVENCE should be used only when a bacterial infection is confirmed or strongly suspected. Inappropriate use may contribute to the emergence of resistant organisms.
Safety Profile and Contraindications
The most commonly reported adverse reactions in clinical studies, occurring in at least 2% of patients, included headache, dizziness, nausea, and diarrhea. Laboratory abnormalities such as neutropenia and leukopenia were also observed.
NUZOLVENCE is contraindicated in patients with a known hypersensitivity to zoliflodacin. Additionally, concomitant use with moderate or strong CYP3A4 inducers is contraindicated, as these agents may significantly reduce plasma concentrations of zoliflodacin and diminish therapeutic efficacy.
Warnings and Precautions
Based on animal studies, NUZOLVENCE carries important safety warnings:
- Embryo-fetal toxicity: Use during pregnancy should be avoided, as zoliflodacin may cause fetal harm at clinically relevant doses.
- Reproductive risks: Animal data suggest a potential increased risk of early pregnancy loss in female partners of treated males. Male patients with female partners of reproductive potential are advised to use effective contraception for at least three months following treatment.
- Testicular toxicity: Findings from animal studies indicate possible impairment of male fertility. Human spermatogenesis studies have not been conducted.
- Hypersensitivity reactions: Rash and pruritus have been reported. Therapy should be discontinued if allergic reactions occur.
- Clostridioides difficile infection: As with many antibacterial agents, NUZOLVENCE may be associated with CDI, ranging from mild diarrhea to severe colitis.
Use in Specific Populations
NUZOLVENCE has not been established as safe or effective in pediatric patients younger than 12 years or weighing less than 35 kg. Clinical trials also included limited numbers of patients aged 65 years and older, making it unclear whether older adults respond differently than younger populations.
There are no available data on the presence of zoliflodacin in human or animal milk, and the effects on breastfeeding infants remain unknown.
Commercialization Plans
Innoviva Specialty Therapeutics plans to commercialize NUZOLVENCE in the second half of 2026, either independently or in partnership with a commercialization collaborator. The company aims to support responsible access to this new therapy while aligning with global antimicrobial stewardship efforts.
Reporting Adverse Events
Healthcare professionals and patients are encouraged to report adverse reactions associated with NUZOLVENCE to either Innoviva Specialty Therapeutics or the FDA’s MedWatch program. Additional safety monitoring includes a postmarketing pregnancy safety study.
Looking Ahead
The FDA approval of NUZOLVENCE marks a significant advance in the fight against gonorrhea and antibiotic resistance. With its single-dose oral administration, novel mechanism of action, and demonstrated efficacy against resistant strains, NUZOLVENCE offers a new option for clinicians and patients facing a persistent and evolving public health threat.
As global health authorities continue to emphasize the urgent need for new antibiotics, NUZOLVENCE stands as an important example of how collaboration, innovation, and scientific rigor can deliver meaningful solutions to longstanding infectious disease challenges.
About Innoviva Specialty Therapeutics
Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc., is focused on delivering innovative therapies in critical care and infectious disease. Innoviva Specialty Therapeutics’ products, through its affiliate, La Jolla Pharmaceutical Company, include GIAPREZA® (angiotensin II), approved to increase blood pressure in adults with septic or other distributive shock, and XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections in adults. Innoviva Specialty Therapeutics’ products, through its affiliate, Entasis Therapeutics Inc., include XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use approved for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter), and NUZOLVENCE® (zoliflodacin), a first-in-class, single-dose, oral antibiotic FDA-approved for the treatment of uncomplicated urogenital gonorrhea, including strains resistant to current first-line therapies. Through a licensing agreement with Basilea Pharmaceutica, Ltd., Innoviva Specialty Therapeutics retains U.S. marketing rights for ZEVTERA® (ceftobiprole), the only FDA-approved cephalosporin specifically designed to treat adult patients with acute bacterial skin and skin structure infections (ABSSSI), adult patients with Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, and adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia (CABP).
About GARDP
The Global Antibiotic Research & Development Partnership (GARDP) is a not-for-profit global health organization driven to protect people from the rise and spread of drug-resistant infections, one of the biggest threats to us all. By forging the public-private partnerships that matter, we develop and make antibiotic treatments accessible to people who need them. Vital support for our work comes from the governments of Canada, Germany, Japan, Monaco, the Netherlands, Switzerland, the United Kingdom, the Canton of Geneva, the European Union, as well as the Gates Foundation, Global Health EDCTP3, GSK, the RIGHT Foundation, the South African Medical Research Council (SAMRC) and Wellcome. GARDP is registered under the legal name GARDP Foundation.
About Innoviva
Innoviva, Inc. is a diversified holding company with a core royalties portfolio, a leading critical care and infectious disease platform known as Innoviva Specialty Therapeutics, and a portfolio of strategic investments in healthcare assets. Innoviva’s royalty portfolio includes respiratory assets partnered with Glaxo Group Limited (“GSK”). Innoviva is entitled to receive royalties from GSK on sales of RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®. Innoviva’s other innovative healthcare assets include infectious disease and critical care assets stemming from acquisitions of Entasis Therapeutics, including XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use approved for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex and NUZOLVENCE® (zoliflodacin), a first-in-class, single-dose, oral antibiotic FDA-approved for the treatment of uncomplicated urogenital gonorrhea, including strains resistant to current first-line therapies, and La Jolla Pharmaceutical Company, including GIAPREZA® (angiotensin II), approved to increase blood pressure in adults with septic or other distributive shock and XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections in adults. Innoviva also markets ZEVTERA (ceftobiprole), an advanced-generation cephalosporin antibiotic, in the U.S. through an exclusive license from Basilea Pharmaceutica International Ltd, Allschwil.
