Azithromycin

16 October 2024 Application supported by positive results from pivotal phase III EAGLE-2 and EAGLE-3 trials 26 March 2025 assigned as action date for FDA decision Gepotidacin could be the first in a new class of oral antibiotic treatment for uUTIs in over 20 years GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for gepotidacin, an investigational, first-in-class oral antibiotic with a novel mechanism of action for the treatment of female adults (≥40 kg) and adolescents (≥12 years, ≥40 kg) with uncomplicated urinary tract infections (uUTIs). The FDA has granted Priority Review for this application and assigned a Prescription Drug User Fee Act (PDUFA) action date of 26 March 2025. Over half of all women are affected by uUTIs in their lifetime1, with approximately 30% suffering from recurrent disease which can cause significant patient burden, including discomfort and restriction of daily activities.2 New treatments are needed as the number of uUTIs caused by drug-resistant bacteria is increasing and can result in higher treatment failure rates.3 Gepotidacin is a late-stage antibiotic in GSK’s growing infectious disease portfolio and could be the first in a new class of oral antibiotics for uUTIs in over 20 years. The NDA is supported by positive results from the pivotal phase III EAGLE-2 and EAGLE-3 trials. In these studies, gepotidacin demonstrated non-inferiority to nitrofurantoin, the current standard of care for uUTI, in female adults (≥40 kg) and adolescents (≥12 years, ≥40 kg) with a confirmed uUTI and a uropathogen susceptible to nitrofurantoin. In EAGLE-3, gepotidacin achieved statistically significant superiority versus nitrofurantoin, demonstrating therapeutic success in 58.5% (162/277) of participants compared to 43.6% (115/264) for nitrofurantoin (treatment difference 14.6%, 95% CI (6.4, 22.8)). In EAGLE-2, gepotidacin demonstrated therapeutic success in 50.6% (162/320) of participants compared to 47.0% (135/287) for nitrofurantoin (treatment difference 4.3%, 95% CI (-3.6, 12.1)). The safety and tolerability profile of gepotidacin in the EAGLE-2 and EAGLE-3 phase III trials was consistent with previous trials of gepotidacin. The most commonly reported adverse events (AEs) in gepotidacin participants were gastrointestinal (GI). Diarrhoea was the most common (16% of participants), followed by nausea (9%). Of the participants who reported GI AEs in the gepotidacin group, the maximum severity were mild (69% Grade 1) and moderate (28% Grade 2). Participants with Grade 3 GI events accounted for 3% of all patients with GI events and occurred in <1% of all participants. There was one drug-related serious adverse event in each treatment arm (gepotidacin and nitrofurantoin) across the two trials. The development of gepotidacin has been funded in part with federal funds from the US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under Other Transaction Agreement number HHSO100201300011C and with federal funds awarded by the Defense Threat Reduction Agency under agreement number HDTRA1-07-9-0002. About the EAGLE (Efficacy of Antibacterial Gepotidacin Evaluated) phase III programme The global phase III clinical programme for gepotidacin in adults and adolescents consists of three trials: EAGLE-2 and EAGLE-3 (non-inferiority uUTI trials) compared the efficacy and safety of gepotidacin (1,500mg administered orally twice daily for five days) to nitrofurantoin (100mg administered orally twice daily for five days) with 1531 and 1605 female adults and adolescents with uncomplicated urinary tract infections, respectively. Across both trials, the duration of follow-up for participants was approximately 28 days, and the primary endpoint was the combined clinical and microbiological response at the Test-of-Cure (ToC) visit (days 10-13) in patients with qualifying uropathogens susceptible to nitrofurantoin. EAGLE-1 (non-inferiority urogenital gonorrhoea trial) compared the efficacy and safety of gepotidacin to ceftriaxone plus azithromycin in 628 patients with uncomplicated urogenital gonorrhoea caused by Neisseria gonorrhoeae. About gepotidacin Gepotidacin, discovered by GSK scientists, is an investigational bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct binding site, a novel mechanism of action and for most pathogens, provides well-balanced inhibition of two different Type II topoisomerase enzymes. This provides activity against most target uropathogens (such as E. coli and S. saprophyticus), and N. gonorrhoeae, including isolates resistant to current antibiotics. Efficacy and safety in patients have been demonstrated in uUTI and gonorrhoea phase III clinical trials, including those with drug-resistant pathogens. Due to the well-balanced inhibition, gepotidacin target-specific mutations in both enzymes are needed to significantly affect susceptibility to gepotidacin. Therefore, leading to a lower potential for resistance development. GSK in infectious diseases GSK has pioneered innovation in infectious diseases for over 70 years, and the Company’s pipeline of medicines and vaccines is one of the largest and most diverse in the industry, with a goal of developing preventive and therapeutic treatments for multiple disease areas or diseases with high unmet needs globally. GSK’s expertise and capabilities in innovation, access and stewardship position the Company uniquely to help prevent and mitigate the challenge of antimicrobial resistance. In antimicrobials, in addition to gepotidacin, GSK entered into an exclusive licence agreement with Spero Therapeutics, Inc. in September 2022 to add tebipenem HBr, a late-stage antibiotic and potential treatment for complicated urinary tract infections (cUTIs), to the pipeline and are currently enrolling for PIVOT-PO, a phase III trial. In March 2023, GSK announced an exclusive licence agreement with Scynexis for Brexafemme (ibrexafungerp tablets), a first-in-class antifungal for the treatment of vulvovaginal candidiasis (VVC) and reduction in the incidence of recurrent VVC. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q2 Results for 2024. References You might also like

MONDAY, Aug. 12, 2024 -- Does your kid suffer from wheezing that returns again and again? They might be suffering from a “silent” viral lung infection that would be better treated by changing up their medications, a new study finds. Nearly a quarter of children and teens with severe wheezing have undetected lung infections, researchers reported recently in the Journal of Allergy and Clinical Immunology . Unfortunately, these infections won’t respond to corticosteroids commonly used to treat wheezing, researchers said. In fact, higher doses of steroids might put children at higher risk of lingering lung inflammation, as well as other known side effects of those drugs. “While steroids can help some children with wheeze, many children in the study showed no patterns of inflammation that would improve with steroids,” said lead researcher Dr. Gerald Teague , a pediatric pulmonologist with the University of Virginia School of Medicine. Instead, these kids should be treated with medications that target viruses and symptoms of viral infection, Teague said. “I advise the parents of my patients that have wheeze episodes that are triggered by colds should be treated with anti-inflammatory medications that build immunity to viruses, such as azithromycin ,” Teague said in a university news release. "They look surprised that we would use an antibiotic for a viral infection, but, in fact, azithromycin bolsters the immune response to viruses in a positive way,” Teague added. For the study, researchers screened more than 800 children and teens with severe and persistent wheezing -- a whistling or rattling sound that occurs while breathing. Rhinoviruses -- the main cause of the common cold -- can trigger wheezing episodes, but wheezing more often is treated the same as asthma, researchers said. In asthma , inhaled corticosteroids are used to reduce airway inflammation. But the results showed that 22% of children with recurrent wheezing were indeed suffering from silent viral infections. Researchers aren’t sure why these kids can’t shake off these infections, which also can involve other types of viruses. They suspect something may be going awry in the immune cells of the children’s lungs, so that they are unable to fight off these viruses. Notably, the problem seems to primarily affect very young children, researchers said. By the time they reach school age, viral-associated wheezing becomes less common. Doctors should rethink how they treat recurrent wheezing and explore potential causes before prescribing powerful corticosteroids, Teague said. “Viral infections are the most important trigger of acute wheeze episodes in children and, in some cases, lead to respiratory distress and hospital care,” Teague said. “We hope this discovery will stimulate further work in the treatment of recurrent wheeze and viral infections in children,” Teague added. “The field has to get to away from overuse of potentially toxic steroids for the treatment of acute wheeze to include novel therapies which target specific patterns of inflammation.” Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.