The new antibiotic combination cefepime/enmetazobactam (brand name Exblifep) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of complicated urinary tract infections (cUTI), its manufacturer Advanz Pharma has announced.
The intravenous formulation is a fixed-dose combination of enmetazobactam – a novel extended-spectrum-lactamase inhibitor belonging to the penicillanic acid sulfone class – with the 4th generation cephalosporin cefepime.
This enhances the efficacy of cefepime against resistant bacteria, including extended spectrum beta-lactamase (ESBL)-producing pathogens.
Cefepime/enmetazobactam has been given the green light in the EU for the treatment of adult patients with cUTIs, including pyelonephritis; hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP); and the treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed.
The drug was designed as a new antibiotic combination to combat the growing antimicrobial resistance in Gram-negative bacteria, Advanz Pharma said.
Treatment superiority of cefepime/enmetazobactam
The CHMP recommendation was based on the results of the phase 3 randomised, double-blind, multi-centre ALLIUM trial, which was undertaken at 112 sites in 19 countries.
The trial considered how the efficacy of cefepime/enmetazobactam compared with piperacillin/tazobactam for the treatment of cUTIs or acute pyelonephritis (AP) and the primary efficacy outcome was clinical cure and microbiological eradication.
Eligible patients were randomised to receive either cefepime, 2 g/enmetazobactam, 0.5 g (n = 520), or piperacillin, 4 g/tazobactam, 0.5 g (n = 521), by two-hour infusion every eight hours for seven days (up to 14 days in patients with a positive blood culture at baseline).
Cefepime/enmetazobactam demonstrated statistically significant superior overall treatment success (clinical cure combined with microbiological eradication) at a test-of-care visit compared with piperacillin/tazobactam in cUTI, including AP, caused by Gram-negative pathogens (79.1% vs 58.9%).
Statistically significantly superior results were also observed among patients with infections caused by ESBL-producing pathogens (73.7% vs 51.5%, respectively).
Cefepime/enmetazobactam demonstrated a tolerable safety profile, comparable to piperacillin/tazobactam.
Treatment-related serious adverse events were reported in 0.2% of patients treated with cefepime/enmetazobactam versus 0.6% of patients treated with piperacillin/tazobactam.
The European Medicines Agency noted the most common side effects as pain and inflammation at the infusion site, diarrhoea, skin rash and headache.
According to Advanz Pharma, cefepime/enmetazobactam has shown promising in vitro activity against the more resistant beta-lactamase mutations OXA-48 and AmpC, which are increasing in Europe and for which there are few therapeutic alternatives.