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Natural Enemy Shown Effective Against Staph Bacteria

MRSA bacteria

Methicillin-resistant Staphylococcus aureus, or MRSA, bacteria (

5 Feb. 2019. A clinical trial shows adding a treatment for drug-resistant infections based on the bacteria’s natural enemies kills more Staphylococcus aureus bacteria than standard antibiotics alone. Results of the trial were released last month testing the drug called exebacase, made by the biotechnology company ContraFect Corp. in Yonkers, New York, based on earlier research conducted at Rockefeller University in New York City.

ContraFect licenses work on enzymes known as lysins from the lab of bacteriologist and immunologist Vincent Fischetti at Rockefeller University. Lysins are produced by viruses called bacteriophages, natural enemies of bacteria. Bacteriophages infect and replicate inside bacteria, during which time the viruses produce lysin enzymes. Lysins then break down the walls of bacterial cells, destroying the bacteria.

Fischetti and colleagues study lysins’ activity in bacteria, leading to development of synthetic forms of these enzymes. In tests with lab mice, for example, the researchers found that an engineered lysin could pneumococcal pneumonia infections and reverse lung damage after 1 day. Other studies with mice infected by Staphylococcus aureus, or S. aureus bacteria causing bacteremia, or infections in the blood stream, show an engineered lysin can reverse the infections and rescue the animals.

Based on Fischetti’s work, ContraFect developed exebacase as a treatment for S. aureus infections. Exebacase, formerly code-named CF-301, is designed as a supplement for standard antibiotics to treat bacteremia. The company says exebacase is the only lysin-based treatment now in clinical trials, with the drug shown safe in an early-stage trial. As reported by Science & Enterprise in March 2017, Contrafect was one of a small group of companies to receive grants from The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X, partnership in the U.S. and U.K. to develop treatments and diagnostics to counter antibiotic resistance.

The mid-stage, or phase 2, clinical trial recruited 116 patients with blood stream bacterial infections in U.S., Europe, Latin America, Russia, and Israel, with the vast majority of individuals (79%) in the U.S. Participants were randomly assigned to receive infusions of exebacase with standard antibiotics, or the standard antibiotics with a placebo, with 71 patients receiving exebacase and antibiotics, while 45 receiving antibiotics and placebo. The study team looked primarily for clinical responses to the treatments after 14 days, as well as safety and tolerability experiences of participants, concentrations of the drug in plasma after 2 days, and time needed to clear the drug from the body for up to 2 days.

Initial results reported by ContraFect show overall, more participants responded to exebacase and antibiotics (70%) than standard antibiotics and placebo (60%) after 14 days. The study team also looked responses of participants with methicillin-resistant S. aureus, or MRSA, infections, a dangerous form of resistant staph infections often found in health care facilities, as well as individuals in the trial with endocarditis, infection of the heart’s inner lining, a complication associated with bacteremia.

The results show more patients with MRSA receiving exebacase and antibiotics responding to their treatments after 14 days than those receiving antibiotics and placebo. More participants with endocarditis on the right side of their hearts likewise responded with exebacase and antibiotics than those receiving the placebo. The number of participants with endocarditis on the left side of their hearts was too small to produce statistically reliable results.

Participant groups receiving exebacase and placebo had about the same rate of adverse events of any kind from the treatments, 89 and 85 percent respectively, with the rate of serious adverse effects also about the same, 47 and 51 percent. Among all participants, 19 percent of exebacase recipients and 15 percent of those receiving the placebo died, but ContraFect says the deaths were not a result of the treatments.

The company says results of the study support conducting a late-stage clinical trial that generates findings to take to regulatory authorities. “This is the first time a lysin-based drug has gone this far in clinical development,” says Fischetti in a Rockefeller University statement. “In fact, there is no antibiotic alternative that has ever successfully completed phase 2 trials. More work needs to be done, but this study is very promising.”

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