ContraFect Corporation announced results from a phase 2 study of exebacase for Staph aureus bacterial bloodstream infections have been published in the July 1, 2020 issue of the Journal of Clinical Investigation. The study results established clinical proof-of-concept for exebacase and informed the design of the ongoing Phase 3 DISRUPT (Direct Lysis of Staph aureus Resistant Pathogen Trial) study of exebacase for the treatment of patients with life-threatening Staph aureus bloodstream infections (BSIs), including right-sided endocarditis.
In the Phase 2 superiority-design study, 121 subjects with Staph aureus BSI, including endocarditis, were randomized 3:2 to receive either a single dose of exebacase or placebo. All patients received standard-of-care (SOC) antibiotics. The study evaluated whether the addition of exebacase to SOC antibiotic therapy improved clinical response rates compared to treatment with SOC antibiotics alone. The primary efficacy endpoint was clinical outcome (responder rate) at day 14.
Clinical responder rates at day 14 were 70.4% and 60.0% in the exebacase + antibiotics and antibiotics alone groups, respectively and were 42.8 percentage points higher in the pre-specified MRSA subgroup. Treatment with exebacase was also associated with a 21-percentage point reduction in the 30-day all-cause mortality, a four-day reduction in median length of hospital stay, and meaningful reductions in 30-day hospital readmission rates in MRSA-infected patients. Exebacase was generally safe and well tolerated, with adverse events consistent with those expected in critically ill, hospitalized patients with potentially life-threatening S. aureus BSI, including endocarditis and/or underlying comorbid conditions.
The phase 3 DISRUPT trial is a randomized, double-blind, placebo-controlled clinical study conducted in the U.S. to assess the efficacy and safety of exebacase in approximately 350 patients with complicated Staph aureus bacteremia, including right-sided endocarditis. Patients enrolled in the Phase 3 study will be randomized 2:1 to receive either exebacase or placebo, with all patients receiving SOC antibiotics. The primary efficacy endpoint will be clinical response at Day 14 in patients with MRSA bacteremia, including right-sided endocarditis. The principal investigator is Dr. Vance Fowler, Professor of Medicine in the Division of Infectious Diseases at Duke University.
About Exebacase (CF-301)
Exebacase is a recombinantly-produced lysin (cell wall hydrolase enzyme) with potent bactericidal activity against Staph aureus, a major cause of bloodstream infections (BSIs) also known as bacteremia. It has a novel, rapid, and specific mechanism of action that targets the peptidoglycan cell wall that is vital to Staph aureus bacteria. In addition, in vitro and in vivo experiments have shown that exebacase is highly active against biofilms which complicate Staph aureus infections. Exebacase was licensed from The Rockefeller University and is being developed at ContraFect. The FDA has granted Breakthrough Therapy designation.