Gepotidacin

On consecutive days, the FDA approved two new oral, first-in-class antibiotics for the treatment of gonorrhea. After a three-decade drought of new antibiotics to treat gonorrhea, the FDA has signed off on two first-in-class oral treatments for the sexually transmitted infection (STI), which affects more than 80 million people around the world each year. Friday, the U.S. regulator greenlighted Innoviva’s Nuzolvence (zoliflodacin) for uncomplicated urogenital gonorrhea. The nod comes less than 24 hours after the agency granted an approval in the same indication to GSK’s Blujepa, which was already on the market for uncomplicated urinary tract infections following its approval in March.The endorsements are similar in that both therapies are indicated for those ages 12 and older where standard of care treatment is contraindicated or where patients are intolerant or unwilling to use the first line of treatment.While the clearance for Nuzolvence covers patients weighing at least 35 kg (77 pounds), patients must weigh at least 99 pounds to start on Blujepa, according to the FDA..The approvals come at an important juncture as antimicrobial resistance to gonorrhea treatment has been growing. Gonorrhea has been recognized by the World Health Organization and the U.S. Centers for Disease Control and Prevention (CDC) as a priority pathogen and an urgent public threat.The development of Nuzolvence was part of a private, not-for-profit collaboration with the Global Antibiotic Research and Development Partnership (GARDP), which sponsored and conducted the phase 3 clinical trial on which FDA approval was based. “This approval marks a huge turning point in the treatment of multidrug-resistant gonorrhoea, which until now has been outpacing antibiotic development,” Manica Balasegaram, M.D., executive director of the GARDP, said in a release. “Zoliflodacin shows that a different public-private partnership approach to antibiotic development is possible—one that prioritizes global health needs, strengthens access where the burden is highest, and protects the effectiveness of new drugs for the long-term.” The approval for Innoviva comes one day after the company published (PDF) results in The Lancet from a phase 3 trial demonstrating the noninferiority of Nuzolvence to the standard care combination treatment of injected ceftriaxone and oral azithromycin.“A new antibiotic that does not require injection and can be used for patients who are allergic to penicillin or related drugs meets two important unmet needs in the treatment of gonorrhea.," lead trial investigator Edward Hook III, M.D., of the University of Alabama at Birmingham, said in a release. Innoviva asserts that its study of 930 patients is the largest ever conducted for a new treatment against Neisseria gonorrhoeae, the bacteria behind gonorrhea. The program included 16 trial sites in five countries—Belgium, the Netherlands, South Africa, Thailand and the U.S.—in five different global regions where there is a high prevalence of the STI.“As clinicians, we see the devastating impact drug-resistant gonorrhoea can have on people’s lives in Thailand,” Rossaphorn Kittiyaowamarn, M.D., the principal Investigator for Bangrak STI Medical Center, said in a release. “With the number of cases on the rise, there is also huge value in carrying out trials in high-burden countries and among high-burden populations to bring about effective treatment options." If left untreated or inadequately treated, gonorrhea can lead to infertility and other sexual and reproductive health issues. In 2023, there were more than 600,000 cases of gonorrhea in the U.S., according to the CDC, making it the second-most common STI after chlamydia.  For its part, Innoviva traces its roots to 1996, when it was established as a royalty management company called Advanced Medicine. It rebranded with its current name in 2016. Over a span of two months in 2022, the company bought out La Jolla and Entasis and combined them to form a subsidiary, Innoviva Specialty Therapeutics, to commercialize critical care and infectious disease treatments. “The FDA’s approval of Nuzolvence marks a pivotal moment for patients and the broader healthcare community managing gonorrhea infections,” Pavel Raifeld, CEO of Innoviva, said in a statement. “This achievement reflects the strength of our development capabilities and the impact of our collaboration with GARDP and the global scientific community.”

GSK has secured an FDA label expansion for its antibiotic Blujepa to treat patients with gonorrhea. In March of this year, the U.S. regulator signed off on Blujepa as a treatment for uncomplicated urinary tract infections. With an increase in the antimicrobial resistance to therapies for gonorrhea, doctors have been left with fewer options to treat the sexually transmitted infection (STI), which strikes more an 80 million annually around the world.Thursday, the FDA addressed the shortfall with a label expansion for GSK’s Blujepa. The U.S. approval brings a new class of antibiotic treatment to gonorrhea for the first time in more than three decades. It also provides an oral option versus the injected therapies currently used to combat the infection.Blujepa already is on the market, as the U.S. regulator endorsed it in March of this year for an array of uncomplicated urinary tract infections.As for the gonorrhea nod, the FDA has cleared its use for those age 12 and older and who weigh at least 45 kg (100 pounds) in cases where standard of care (SOC) is contraindicated or in cases where patients are intolerant or unwilling to use the first line of treatment.Paving the way for the approval was a phase 3 trial which showed Blujepa was noninferior to the SOC combination therapy of intramuscular ceftriaxone plus oral azithromycin. The SOC antibiotics were originally approved by the FDA in 1982 and 1991, respectively. The study also demonstrated the safety and tolerability of the treatment, with mild to moderate gastrointestinal issues reported as the most common adverse reactions.Tyler Evans, M.D., an infectious disease specialist and the CEO of the Wellness Equity Alliance, called the approval a “rare moment of progress in the fight against antibiotic resistance.”“A first-in-class oral treatment for gonorrhea is a major scientific achievement, especially for a pathogen that has outsmarted nearly every drug we have used against it. Expanding treatment options matters, particularly for patients who face barriers to injectable therapy or have limited alternatives,” Evans added. If left untreated or inadequately treated, gonorrhea can lead to infertility and other sexual and reproductive health issues. In 2023, there were more than 600,000 cases of gonorrhea in the U.S., according to the Centers for Disease Control and Prevention (CDC), making it the second-most common STI after chlamydia. There is no vaccine in the U.S. for the prevention of gonorrhea, which is spread by unprotected sex and can affect the genitals, rectum, eyes and throat.Gonorrhea has been recognized by the World Health Organization and the U.S. CDC as a priority pathogen and an urgent public threat. The development of Blujepa was funded in part by the U.S. Department of Health and Human Services, the Administration for Strategic Preparedness and Response and the Biomedical Advanced Research and Development Authority, GSK said. Another oral antibiotic to treat gonorrhea is on the doorstep of approval in the U.S. as Massachusetts company Innoviva Specialty Therapeutics faces a Monday FDA decision date for zoliflodacin. Thursday, the company revealed (PDF) results from a phase 3 trial which showed the noninferiority of zoliflodacin to the ceftriaxone/azithromycin combo.