Positive Results for Cefepime-Enmetazobactam in Phase 3 Trial

More than 100 million people around the world are impacted by complicated urinary tract infections each year, leading to sizable social costs and health burden on patients. Additionally, the global rise of antimicrobial resistance among gram-negative pathogens is a concerning problem suggesting the need for new treatment options.

Allecra Therapeutics has announced that its investigational antibiotic combination cefepime-enmetazobactam met the European Medicines Agency and US Food and Drug Administration (FDA) pre-specified primary endpoint in the phase 3 ALLIUM clinical trial.

The combination features enmetazobactam, a novel extended-spectrum β-lactamase inhibitor, and cefepime, a fourth-generation cephalosporin.

The ALLIUM trial compared cefepime-enmetazobactam to piperacillin-tazobactam in patients with complicated urinary tract infections, including acute pyelonephritis.

In addition to meeting its primary endpoint, cefepime-enmetazobactam displayed superiority over piperacillin-tazobactam alongside a comparable safety profile.

The phase 3 study was was a multicenter, randomized, controlled, double-blind, global investigation across 112 sites within 19 countries.

The investigators enrolled 1034 patients who were randomized to receive either cefepime 2g/ enmetazobactam 0.5 g or piperacillin 4 g/ tazobactam 0.5 g every 8 hours as a 2-hour continuous intravenous infusion.

The primary endpoint was defined by both clinical cure as reflected by symptom resolution and microbiological eradication at the test-of-cure visit.

Overall success was 79.1% for cefepime-enmetazobactam compared with 58.9% for piperacillin-tazobactam (adjusted stratified difference, 21.2% [95% stratified Newcombe Confidence Interval, 14.3% to 27.9%]).

Treatment discontinuation was comparable in both drug combinations, at 5.2% in cefepime-enmetazobactam and 4.0% in piperacillin-tazobactam. Serious adverse events were reported by 4.3% of patients in the cefepime-enmetazobactam group and 3.7% of patients in the piperacillin-tazobactam group.

Allecra’s investigational cefepime-enmetazobactam drug has been granted Qualified Infectious Disease Product and Fast Track Designation by the FDA, which provides priority FDA review and 5 years of added market exclusivity.

The European Medicines Agency indicated that Allecra Therapeutics would be permitted to seek approval of the drug combination for use in pneumonia, including health care-acquired pneumonia and ventilator-acquired pneumonia, without conducting a phase 3 study in the pneumonia indication.

“According to most recent U.S. Centre for Disease Control and Prevention data 197,400 cases of ESBL-producing Enterobacteriaceae occur every year with 9100 associated deaths. The use of piperacillin-tazobactam for the treatment of such infections has been controversial, and the development of new treatments for these infections has been classified as a critical priority by the World Health Organization,” said Keith Kaye MD, MPH, Professor of Medicine and Director of Research for Infectious Diseases at University of Michigan, in the press release.

“Cefepime-enmetazobactam combination may provide a novel therapeutic option addressing this serious threat.”