Phase 2 study results demonstrated the potential clinical benefit of exebacase, when used in addition to existing antibiotics, for the treatment of life-threatening MRSA bacteremia
Exebacase Phase 2 study results supported FDA Breakthrough Therapy designation and the design of the ongoing Phase 3 DISRUPT study
YONKERS, N.Y., June 17, 2020 (GLOBE NEWSWIRE) -- ContraFect Corporation (CFRX), a clinical-stage biotechnology company focused on the discovery and development of direct lytic agents (DLAs), including lysins and amurin peptides, as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections, today announced the publication of the exebacase Phase 2 study results 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.
“This is an important study. Complicated Staph aureus bloodstream infections are common, potentially lethal and currently available antibiotic treatments are suboptimal. Innovative new therapeutic approaches are desperately needed. The exebacase Phase 2 study demonstrated meaningful improvements in clinical outcomes among patients who received exebacase and I look forward to the results of the ongoing Phase 3 superiority study,” said Vance Fowler, M.D., Study Principal Investigator and Professor of Medicine of Duke University School of Medicine.
“The publication of the exebacase Phase 2 study results in the prestigious Journal of Clinical Investigation provides recognition of the novelty and importance of this potential new therapeutic approach for life-threatening infections. This first ever demonstration of the potential clinical utility of lysins supported the FDA Breakthrough Therapy designation, and we look forward to working closely with the FDA under this designation as we progress the program towards BLA submission,” said Cara Cassino, M.D., Chief Medical Officer and Executive Vice President of Research and Development at ContraFect.
Summary of the Exebacase Phase 2 Trial
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 (p-value=0.314), and were 42.8 percentage points higher in the pre-specified MRSA subgroup (p-value=0.010). Treatment with exebacase was also associated with a 21-percentage point reduction in the 30-day all-cause mortality (p=0.056), 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. Rates of adverse events (AEs) were similar in both groups. There were no serious AEs determined to be related to exebacase, no reports of hypersensitivity related to exebacase and no patients discontinued treatment with study drug in either treatment group.
The Phase 3 DISRUPT study of exebacase 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. Secondary endpoints will include clinical response at Day 14 in the All Staph aureus patients (MRSA and methicillin-sensitive Staph aureus (MSSA)), 30-day all-cause mortality in MRSA patients, and clinical response at Day 30 and Day 60 in both MRSA and All Staph aureus patients. Health resource utilization, including length of hospital stay, length of time in ICU and 30-day hospital readmission rates, will also be evaluated. The company plans to conduct an interim futility analysis following the enrollment of approximately 60% of the study population. 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. Exebacase has the potential to be a first-in-class treatment for Staph aureus 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.
ContraFect is a biotechnology company focused on the discovery and development of direct lytic agents (DLAs), including lysins and amurin peptides, as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections. An estimated 700,000 deaths worldwide each year are attributed to antimicrobial-resistant infections. We intend to address life threatening infections using our therapeutic product candidates from our platform of DLAs, which include lysins and amurin peptides. Lysins are a new class of DLAs which are recombinantly produced antimicrobial proteins with a novel mechanism of action associated with the rapid killing of target bacteria, eradication of biofilms and synergy with conventional antibiotics. Amurin peptides are a novel class of DLAs which exhibit broad-spectrum activity against a wide range of antibiotic-resistant Gram-negative pathogens, including Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii, and Enterobacter species. We believe that the properties of our lysins and amurin peptides will make them suitable for targeting antibiotic-resistant organisms, such as MRSA and P. aeruginosa, which can cause serious infections such as bacteremia, pneumonia and osteomyelitis. We have completed a Phase 2 clinical trial for the treatment of Staph aureus bacteremia, including endocarditis, with our lead lysin candidate, exebacase, which is the first lysin to enter clinical studies in the U.S. Exebacase, currently being studied in a pivotal Phase 3 clinical study, was granted Breakthrough Therapy designation by the FDA for the treatment of MRSA bloodstream infections (bacteremia), including right-sided endocarditis, when used in addition to standard-of-care anti-staphylococcal antibiotics in adult patients.
This press release contains, and our officers and representatives may make from time to time, “forward-looking statements” within the meaning of the U.S. federal securities laws. Forward-looking statements can be identified by words such as “projects,” “may,” “will,” “could,” “would,” “should,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” “promise” or similar references to future periods. Examples of forward-looking statements in this release include, without limitation, statements regarding ContraFect’s ability to discover and develop DLAs as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections, statements made by Dr. Pomerantz and Dr. Cassino, statements regarding the Phase 2 trial results and exebacase, whether the Phase 2 results demonstrated clinical benefit and supported Breakthrough Therapy designation, whether exebacase has the potential to be a first in class treatment for Staph aureus bacteremia, ContraFect’s ability to address life threatening infections using its DLA platform, whether lysins are a new class of DLAs which are recombinantly produced, antimicrobial proteins with a novel mechanism of action associated with the rapid killing of target bacteria, eradication of biofilms and synergy with conventional antibiotics, whether amurins exhibit broad-spectrum activity against a wide range of antibiotic-resistant Gram-negative pathogens, and whether the properties of ContraFect’s lysins and amurins will make them suitable for targeting antibiotic-resistant organisms, such as MRSA and P. aeruginosa. Forward-looking statements are statements that are not historical facts, nor assurances of future performance. Instead, they are based on ContraFect’s current beliefs, expectations and assumptions regarding the future of its business, future plans, strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent risks, uncertainties and changes in circumstances that are difficult to predict and many of which are beyond ContraFect’s control, including those detailed under the caption “Risk Factors” in ContraFect's filings with the Securities and Exchange Commission. Actual results may differ from those set forth in the forward-looking statements. Important factors that could cause actual results to differ include, among others, our ability to develop treatments for drug-resistant infectious diseases. Any forward-looking statement made by ContraFect in this press release is based only on information currently available and speaks only as of the date on which it is made. Except as required by applicable law, ContraFect expressly disclaims any obligations to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
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