The emergence of antibiotic-resistant “superbugs” underscores the need for new drugs and therapies for protecting the public from pathogenic organisms. Since bacteria rapidly evolve to evade the action of new antibiotics, the drugs quickly lose their effectiveness. The prevalence of MRSA (methicillin-resistant Staphylococcus aureus) illustrates the severity of the problem.
A novel approach to the “antibiotic problem,” interestingly, is not an antibiotic at all but a new class of anti-microbial agent known as aganocides. Developed by Emeryville, California-based Novabay Pharmaceuticals, aganocides provide fast, efficient killing of most infectious bacteria but lack the potential to cause resistance in target organisms.
On October 25, Dr. Barbara Belisle, Director, Microbiology and Cell Biology at Novabay, discussed new data on the effectiveness of her company’s lead aganocide agent, NVC-422. Poster presentation F1-3940, Novel N-Chlorotaurine Derivatives as Topical Antimicrobials, describes key milestones in the development of NVC-422. The poster session was held at the 48th Annual Interscience Conference on Antimicrobials Agents and Chemotherapy (ICCAC) in the Walter E. Washington Convention Center in Washington, DC. More than 12,000 physicians, researchers, and other health care professionals from around the globe gather at IACC to review the latest scientific and clinical findings on infectious diseases.
NVC-422 belongs to a class of chemical anti-microbial agents known as N-chlorotaurines, which are found in most higher organisms. Since endogenous chlorotaurines are chemically labile, Novabay created a more stable, commercially viable version of these agents by modifying the natural chemical’s structure. NVC-422 is not an antibiotic, but an anti-microbial that kills pathogens on contact through the release of highly reactive chlorine species.
The anti-microbial activity of NVC-422 is strongly pH-dependent, with the lowest MBC (minimum bactericidal concentration) at around pH 4 for S. aureus and E. coli. The agent is effective at physiologic pH as well, but at higher concentration. However, even this high dose is well below levels that might cause side effects when applied to the skin or other tissues.
NVC-422 shows broad activity against Gram negative and Gram positive bacteria, as well as yeast and biofilm. Novabay scientists have demonstrated three-log reduction of common pathogenic microorganisms at concentrations well within a reasonable therapeutic range. Organisms tested include pathogens that cause influenza, pneumonia, and infections of the skin and sinuses, as well as disease-causing yeasts.
In studies comparing NVC-422 directly against common topical anti-microbial agents, the aganocide showed a therapeutic index that was up to 100 times higher than those of the conventional agents. Therapeutic index, a measure of a drug’s safety, is the ratio of effective dose to the dose that causes side effects.
Safety and efficacy are paramount in the development of any new drug, but the true test of an anti-microbial agent is the ability of organisms encountering it to develop resistance. In numerous studies of NVC-422 in various organisms at sub-lethal concentrations, essentially none of the organisms adapted to the drug. Just as significant was the lack of any identifiable cross-resistance from Gram positive and Gram negative organisms known to be immune to clinically used antibiotics.
One lead application of NVC-422 is the prevention and elimination of biofilms – bacterial colonizations that develop in catheters and other implantable medical devices. Novabay has made urinary catheter biofilm eradication a top priority. At pharmacologically meaningful concentrations, NVC-422 exhibits a high kill rate against common urinary bacterial pathogens while showing almost zero toxicity toward cultured bladder cells.
“We are proud of the progress we have made in our research and clinical development of antimicrobial compounds and are delighted to have been asked to present an oral summary at this prestigious meeting,” said Dr. Ron Najafi, CEO of Novabay Pharmaceuticals. “We would like to acknowledge the contributions of NovaBay scientists whose innovative work is partly summarized in these posters. We continue to discover new characteristics of these Aganocide® compounds, enabling us to further expand the number of potential indications where they may help improve people’s health and ultimately save lives.”
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