Favourable opinion for reimbursement in the following MA indications: “in adults, in the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP), as well as in the treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above”, only as a last resort, for the treatment of patients with infections caused by Enterobacterales with an OXA-48-type resistance mechanism associated with ESBL, susceptible to the combination, particularly in the context of a carbapenem-sparing strategy.
Unfavourable opinion for reimbursement in the other situations covered by the MA indication.
Clinical Benefit
Substantial
The clinical benefit of EXBLIFEP (cefepime/enmetazobactam) 2 g/0.5 g powder for concentrate for solution for infusion is substantial in adults, in the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP), as well as in the treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above, only as a last resort, for the treatment of patients with infections caused by Enterobacterales with an OXA-48-type resistance mechanism associated with ESBL, susceptible to the combination, particularly in the context of a carbapenem-sparing strategy.
Insufficient
The clinical benefit of EXBLIFEP (cefepime/enmetazobactam) 2 g/0.5 g powder for concentrate for solution for infusion is insufficient to justify public funding in view of the available alternatives in the other MA situations.
Clinical Added Value
no clinical added value
Considering:
its activity demonstrated in vitro on Gram-negative bacteria, such as Enterobacterales with an OXA-48-type resistance mechanism and extended-spectrum beta-lactamases (ESBL);
experience acquired with cefepime, a fourth-generation cephalosporin widely used in the treatment of severe hospital-acquired infections due to Gram-negative bacteria with high suspicion of P. aeruginosa;
the results of the phase 3 study (ALLIUM) having demonstrated its non-inferiority compared to the piperacillin/tazobactam combination, then its superiority for the composite endpoint of clinical cure and microbiological eradication at the test-of-cure visit (m-MITT population): 273/345 (79.1%) versus 196/333 (58.9%); i.e. a difference between the 2 groups of 21.2%; (95% CI: [14.3%, 27.9%]) in adult patients 18 years of age or older, with a clinical diagnosis of complicated urinary tract infection or acute pyelonephritis due to Gram-negative urinary pathogens;
limited clinical data in severe forms and/or forms due to multi-drug resistant bacteria;
the absence of a clinical study in hospital-acquired pneumonia, including ventilator associated pneumonia, with the efficacy being extrapolated from PK/PD data and clinical data for cefepime alone;
the fact that the cefepime/enmetazobactam combination is one of the few current antibiotics active for the treatment of Enterobacterales with an OXA-48-type resistance mechanism associated with ESBL, particularly in the context of a carbapenem-sparing strategy,
the Committee deems that EXBLIFEP (cefepime/enmetazobactam) provides no clinical added value (CAV V) in the management of complicated urinary tract infections (including pyelonephritis) and hospital-acquired pneumonia (including ventilator associated pneumonia), as well as in the treatment of patients with associated, or suspected of being associated, bacteraemia, as a last resort, for the treatment of patients with infections caused by Enterobacterales with an OXA-48-type resistance mechanism associated with ESBL, susceptible to the combination, particularly in the context of a carbapenem-sparing strategy.
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