Final phase III ALLIUM data in is published in JAMA: Cefepime/Enmetazobactam met criteria for superiority. -Allecra Therapeutics .

The publication represents the first full analysis of the completed Phase III program, which showed that cefepime/enmetazobactam met criteria for non-inferiority and superiority compared to piperacillin/tazobactam in the primary outcome of clinical cure and microbiological eradication.

Cefepime/enmetazobactam is a novel beta-lactam/beta-lactamase inhibitor combination for the treatment of resistant gram-negative infections mediated by Extended Spectrum Beta-Lactamases (ESBLs). In addition to the robust data analysis, the publication highlights the need for novel antibacterial drugs to address antimicrobial resistance, which remains an urgent global public health threat causing an estimated 1.27 million deaths per year worldwide.

The Phase III, randomized, double-blind, active-controlled, multi-center, noninferiority clinical trial was conducted at 90 sites in Europe, North and Central America, South America, and South Africa and enrolled 1,041 adult patients greater than 18 years of age with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by gram-negative urinary pathogens. Eligible patients were randomized to receive either 2 g cefepime/0.5 g enmetazobactam or 4 g piperacillin/0.5 g tazobactam by 2-hour infusion every 8 hours for 7 days. Among patients with cUTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication. The primary outcome occurred in 79.1% (273/345) of patients receiving cefepime/enmetazobactam compared to 58.9% (196/333) receiving piperacillin/tazobactam in the primary analysis data set (between group difference: 21.2% [95% CI, 14.3% to 27.9%]). In the 20.9% (142/678) of patients with an ESBL-producing baseline pathogen, 73.7% (56/76) of patients in the cefepime/enmetazobactam group and 51.5% (34/66) of those in the piperacillin/tazobactam group achieved the composite outcome (difference 30.2% [95% CI, 13.4% to 45.1%]). Treatment-emergent adverse events occurred in 50.0% (258/516) of patients treated with cefepime/enmetazobactam and 44.0% (228/518) with piperacillin/tazobactam; most were mild to moderate in severity (89.9% vs 88.6%, respectively). A total of 1.7% (9/516) of participants who received cefepime/enmetazobactam and 0.8% (4/518) of those who received piperacillin/tazobactam did not complete the assigned therapy due to adverse events.

Keith Kaye M.D., MPH, Chief, Division of Allergy, Immunology and Infectious Diseases at the Robert Wood Johnson Medical School (Rutgers University) and lead author on the publication, commented: “Antimicrobial resistance mediated by ESBLs is a critical clinical challenge and there is a substantial need for novel antibiotics that enable us to effectively treat resistant infections. Cefepime/enmetazobactam has shown improved efficacy compared to a standard of care treatment with a good safety profile. It has the potential to become a replacement for piperacillin/tazobactam and an alternative to the use of carbapenems. I value this opportunity to publish the full data set in JAMA, which underscores the importance of the results.” Patrick Velicitat, MD, Chief Medical Officer of Allecra Therapeutics, stated: “The results of the phase III study suggest that cefepime/enmetazobactam is an appropriate empirical therapy for suspected gram-negative cUTI.”

See "Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis.A Randomized Clinical Trial." Keith S. Kaye, MD; Adam Belley, PhD2; Philip Barth, PhD; et al.JAMA. 2022;328(13):1304-1314. doi:10.1001/jama.2022.17034.