30 August 2019 - - US-based pharmaceutical company VenatoRx Pharmaceuticals has initiated enrollment in its Phase 3 trial of cefepime/VNRX-5133 in patients with complicated urinary tract infections (cUTIs), the company said.

VNRX-5133 is an injectable beta-lactamase inhibitor that features selective and potent in vitro activity against both serine- and metallo-beta-lactamases, including ESBL, OXA, KPC, NDM, and VIM enzymes.

VenatoRx believes that VNRX-5133, in a fixed combination with the fourth generation cephalosporin, cefepime, has the potential to provide a valuable broad-spectrum treatment option to meet unmet medical needs in patients with infections due to carbapenem-resistant pathogens including carbapenem-resistant Enterobacteriaceae and carbapenem-resistant Pseudomonas aeruginosa (CRPA), suspected polymicrobial infections caused by both gram-negative and gram-positive susceptible pathogens, and engineerable bioterror pathogens such as Burkholderia spp.

This Phase 3 clinical trial (ClinicalTrials.gov - NCT03840148) is a global randomized, double-blind, active controlled, non-inferiority study evaluating the efficacy, safety, and tolerability of cefepime/VNRX-5133 in adults with cUTI, including acute pyelonephritis.

The trial will assess the safety and efficacy of cefepime/VNRX-5133 as compared with that of meropenem using clinical cure and microbiological eradication as the primary composite efficacy endpoint. VenatoRx expects to enroll 582 patients for this study, and top-line results are expected by the end of 2020.

Preclinical results showed that cefepime/VNRX-5133 showed potent in vitro activity against all Enterobacteriaceae, with an MIC90of 0.5 mg/L, compared to cefepime, levofloxacin, meropenem, and piperacillin-tazobactam (MIC90 values >128, >4, 4, >64 mg/L, respectively).

Cefepime/VNRX-5133 inhibited 99% of all Enterobacteriaceae at the cefepime dose dependent breakpoint of ≤8 mg/L, including 99% of ESBL-producers and 93% of meropenem-non-susceptible isolates. Cefepime/VNRX-5133 was the most active compound tested against P. aeruginosa, including serine beta-lactamase and MBL-producers.

This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201300019C, The Wellcome Trust under Award No. 360G-Wellcome-101999/Z/13/Z, and the Biomedical Advanced Research and Development Authority, Office of the Assistant secretary for Preparedness and Response, Department of Health and Human Services under Contract No. HHSO100201900007C.

VenatoRx is a private pharmaceutical company that is focused on the discovery and development of novel anti-infectives to treat multi-drug-resistant bacterial infections and hard-to-treat viral infections.

Founded in 2010, VenatoRx has built an in-house R and D organization that has filed over 100 patents spanning multiple research programs.

VenatoRx has received significant funding awards from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health ; Wellcome Trust; the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant secretary for Preparedness and Response at the US Department of Health and Human Service ; the US Department of Defense's Defense Threat Reduction Agency ; and CARB-X, and as well as private equity investments from Versant Ventures, Abingworth and Foresite Capital.