The European Commission has granted marketing authorization for Exblifep*, a fixed-dose antibiotic combination of cefepime and enmetazobactam for the treatment of serious infections. This was announced by Advanz Pharma Holdco Limited, a global pharmaceutical company based in the United Kingdom and with a strategic focus on the supply of specialist, hospital and rare disease medicines in Europe, Canada and Australia, and Allecra Therapeutics, a biopharmaceutical company that develops new therapies to combat antibiotic resistance.
Exblifep – they explain in a note – is approved for the treatment of adult patients with complicated urinary tract infections, including pyelonephritis; hospital-acquired pneumonia, including ventilator-associated pneumonia; bacteremia occurring in definite or suspected association with any of the infections listed above.
Under a licensing and supply agreement concluded in 2022, Advanz Pharma has the rights to develop and commercialize Allecra's antibiotic candidate in the European Union, the United Kingdom, Switzerland and Norway. The drug is a fixed-dose antibiotic combination, administered intravenously, of enmetazobactam, a new broad-spectrum lactamase inhibitor belonging to the penicillanic acid sulphone class, and cefepime, a fourth-generation cephalosporin. Enmetazobactam has been shown to restore the efficacy of cefepime against some multidrug-resistant bacteria, including Esbl-producing pathogens alone or in combination with some resistant mutations of beta-lactamases, such as Oxa-48 or AmpC, which are on the rise in Europe and for which few therapeutic alternatives exist.
Complicated urinary tract infections or cUti, serious and potentially fatal infections – describes the note – represent 19% of all healthcare-associated infections. The range of mortality rates reported in the literature is very wide (2-31%), as it derives from the different composition of the patients included in terms of age, type of infection and comorbidities. Cutis, including acute pyelonephritis (Ap), are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms (fever, chills, malaise, flank pain, back pain), occurring in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization. AP is a bacterial infection that causes inflammation of the kidneys and is one of the most common kidney diseases. It occurs as a complication of an ascending urinary tract infection, which spreads from the bladder to the kidneys and their collecting systems.
Hospital-acquired pneumonia (Hap) and ventilator-associated pneumonia (Vap) are the second most common nosocomial infection (after cUti), as well as a leading cause of death from nosocomial infections in critically ill patients. Hap and Vap are lung infections caused by pathogens acquired during the hospital stay, occurring within 48 hours after hospital admission and which were not incubating at the time of admission.
The new antibiotic combination was tested in Allecra's pivotal phase 3 Allium trial, which compared 1,034 randomized patients who received cefepime 2 g/enmetazobactam 0.5 g or piperacillin 4 g/tazobactam 0.5 g every 8 hours by intravenous infusion continuous 2-hour study in a global, multicenter, randomized, controlled, double-blind study conducted at 112 sites in 19 countries. Exblifep met the primary outcome measure, demonstrating overall statistically significant treatment success (clinical cure combined with microbiological eradication) at the testing visit compared to piperacillin/tazobactam in cUtis, including Ap, caused by Gram-negative pathogens (79 .1% vs 58.9%). Significantly superior results in statistical terms were also observed among patients with infections caused by Esbl-producing pathogens (73.7% vs 51.5%, respectively). The combination demonstrated a tolerable safety profile, comparable to piperacillin/tazobactam: 19.8% vs 14.5%. Treatment-related SAEs (serious adverse effects) were reported in 0.2% of patients treated with Exblifep, compared to 0.6% of patients treated with piperacillin/tazobactam.
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