Allecra Therapeutics announced positive top-line results from the phase 3 ALLIUM trial evaluating Exblifep (cefepime-enmetazobactam) in patients with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). The trial met the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) pre-specified primary endpoint, demonstrating superiority over piperacillin-tazobactam.
The ALLIUM trial was a multi-center, randomized, controlled, double-blind, global study in 112 sites within 19 countries. The trial enrolled 1,034 patients who were randomized to receive either cefepime 2 g/ enmetazobactam 0.5 g or piperacillin 4 g/ tazobactam 0.5 g every 8 hours as a 2 hour continuous intravenous infusion. The primary efficacy endpoint was defined as the composite success outcome of clinical cure (symptoms resolution) and microbiological eradication (< 103 CFU/mL in urine culture) at the test-of-cure visit. The primary efficacy evaluation was performed in the microbiological Modified Intent-to-Treat Population (m-MITT) including patients infected with a Gram-negative pathogen deemed non-resistant to cefepime-enmetazobactam (MIC ≤ 8 mg/L) and piperacillin-tazobactam (MIC ≤ 64 mg/L). There was a prespecified 10% noninferiority margin with superiority to be tested in the event of confirmed noninferiority.
Overall success was 79.1% for Exblifep vs. 58.9% for piperacillin-tazobactam. Treatment discontinuations were seen at comparable levels in 5.2% and 4.0% in Exblifep and piperacillin-tazobactam respectively. Exblifep was well tolerated with 4.3% of patients reporting serious adverse events vs. 3.7 % with piperacillin-tazobactam (0.2% vs. 0.6% assessed as drug related), suggesting comparable safety profile to piperacillin-tazobactam.
Exblifep has been granted Qualified Infectious Disease Product and Fast Track Designation by the US FDA.
About Exblifep (cefepime-enmetazobactam)
Exblifep (cefepime-enmetazobactam) is a combination of enmetazobactam, a novel extended-spectrum β-lactamase inhibitor belonging to the penicillanic acid sulfone class, with the 4th generation cephalosporin cefepime.
About Complicated Urinary Tract Infections
There are approximately 3.6 million patients with cUTIs in the U.S requiring antibiotic therapy. cUTIs, including acute pyelonephritis, are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms, including fever, chills, malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness, that occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization, with treatment typically initiated by IV therapy in a hospital setting.
About Acute Pyelonephritis
AP is a bacterial infection causing inflammation of the kidneys and is one of the most common diseases of the kidney. Pyelonephritis occurs as a complication of an ascending urinary tract infection (UTI) which spreads from the bladder to the kidneys and their collecting systems. Acute pyelonephritis in the United States is found at a rate of 15 to 17 cases per 10,000 females and 3 to 4 cases per 10,000 males annually.