Defensin mimetic · investigational
Brilacidin, development code PMX-30063, is a synthetic small molecule designed to reproduce the properties of host-defense peptides, the natural antimicrobial molecules such as defensins that the immune system uses against microbes. It is not itself a peptide. Trials have tested it against bacterial skin infections, as a rinse to prevent oral mucositis during cancer treatment, and in people hospitalized with COVID-192,3,6.
Many natural host-defense peptides, such as LL-37, carry a positive charge and act on the membranes of microbes1. Brilacidin was designed to capture that behavior on a sturdier non-peptide scaffold. In Staphylococcus aureus it depolarizes the cell membrane to a degree similar to the antibiotic daptomycin, and the bacteria respond with stress programs that point to damage of the cell wall and membrane and to misfolded proteins inside the cell1. Against coronaviruses in cell culture it appears to work in two ways: it damages the virus particle itself, and it binds heparan sulfate on the host-cell surface, which these viruses use as an attachment point, reducing viral entry4,5.
In the laboratory, brilacidin kills a range of Gram-positive and Gram-negative bacteria, including drug-resistant strains1, and it inhibited SARS-CoV-2 in human lung cells and other coronaviruses in cell culture, with added effect when combined with remdesivir4,5. In people, testing has gone no further than phase 2.
A study in acute bacterial skin infections compared several brilacidin regimens with daptomycin, but results are not posted on the trial registry2. In 61 head-and-neck cancer patients receiving chemoradiation, a brilacidin oral rinse was compared with placebo for preventing severe oral mucositis; among evaluable patients, 9 of 21 on brilacidin and 15 of 25 on placebo developed it, and the registry reports no statistical test for that comparison3.
In 120 hospitalized COVID-19 patients, intravenous brilacidin added to standard care did not shorten the time to sustained recovery compared with placebo6.
Brilacidin is not approved by the FDA or any other regulator; it remains an investigational drug.
Human side-effect data come mainly from phase 2 registry results. In the COVID-19 trial, numbness and tingling (hypoesthesia, oral numbness, paresthesia) were reported only in the brilacidin groups, while liver-enzyme rises occurred with both brilacidin and placebo6. In the oral-rinse trial, fatigue, taste changes and dry mouth were reported somewhat more often with brilacidin than placebo, on top of the expected effects of chemoradiation3. Long-term effects are unknown.
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