Brilacidin is a synthetic drug candidate belonging to a class of compounds known as defensin-mimetics. This investigational drug was engineered to replicate the natural antimicrobial properties of the body’s immune system. It acts as a small, non-peptidic molecule modeled after host defense proteins (HDPs), natural peptides of innate immunity. Brilacidin is currently undergoing clinical trials to explore its potential therapeutic applications.
The Mechanism of Brilacidin
Brilacidin disrupts the cell membranes of various pathogens, including bacteria and fungi. Imagine a balloon; brilacidin creates pores and ruptures its surface, causing its contents to spill out. This physical disruption leads to the loss of a microorganism’s function and ultimately its death.
This mechanism contrasts with many traditional antibiotics, which often target specific enzymes or interfere with cellular processes inside the microbe. Brilacidin’s approach, leveraging its cationic and amphipathic properties to bind and integrate into microbial membranes, makes it more challenging for microbes to develop resistance. This is a benefit against antibiotic-resistant “superbugs,” as resistance typically evolves against specific biochemical pathways, not broad physical disruption. Studies show brilacidin causes membrane depolarization in bacteria like Staphylococcus aureus, comparable to other membrane-targeting antibiotics.
Potential Medical Applications
Brilacidin is being investigated for several medical conditions. A primary focus is its most advanced application: preventing and treating severe oral mucositis (OM) in cancer patients. Oral mucositis is a painful and debilitating side effect of chemoradiation therapy, particularly in those undergoing treatment for head and neck cancers. This condition can lead to interruptions in cancer therapy, compromised food and water intake, and in severe cases, even hospitalization.
In clinical trials, an oral rinse formulation of brilacidin demonstrated a reduction in the incidence of severe OM, showing a therapeutic benefit compared to placebo. In one study, the incidence of severe OM was reduced to 36.8% in brilacidin-treated patients, compared to 60.0% in the placebo group. Brilacidin’s dual anti-inflammatory and anti-bacterial properties are suited for addressing the complex pathogenesis of OM.
Beyond oral mucositis, brilacidin has also been studied as a topical antibiotic for acute bacterial skin and skin structure infections (ABSSSI). A Phase 2b trial for ABSSSI indicated that a single intravenous dose of brilacidin yielded comparable clinical outcomes to a seven-day regimen of daptomycin, an FDA-approved antibiotic. Its broader anti-inflammatory and antiviral properties have also led to investigations for other conditions, including inflammatory bowel disease (IBD), where Phase 2 trials have shown promise in achieving clinical remission in a majority of treated patients. Brilacidin has also been explored for its antiviral capabilities, demonstrating inhibition of SARS-CoV-2 in cell culture by disrupting viral integrity and blocking viral entry.
Clinical Development and Safety
The development of a new drug involves a process of clinical trials, progressing through distinct phases. Phase 1 trials focus on safety and dosage, Phase 2 assesses efficacy and further safety, and Phase 3 confirms efficacy and monitors side effects in larger patient populations. Brilacidin has advanced through several of these stages for its various indications.
For the prevention of severe oral mucositis, brilacidin has completed Phase 2 clinical trials, where it reduced the incidence of severe OM. Following these positive results, discussions with the FDA have established a pathway for brilacidin oral rinse to proceed into Phase 3 clinical trials for this indication. In the realm of infectious diseases, brilacidin has completed a Phase 2b trial for acute bacterial skin and skin structure infections. Furthermore, a Phase 2 trial investigating brilacidin for the treatment of hospitalized COVID-19 patients has also been completed, receiving FDA Fast Track designation.
Across these clinical studies, brilacidin has generally exhibited a favorable safety profile and has been well-tolerated by patients. The drug has been tested in human trials involving over 460 subjects, providing a foundation of safety data. Brilacidin remains an investigational drug and has not yet received approval from regulatory bodies like the FDA.