NovaBay Pharmaceuticals Inc., a biotech company developing novel anti-infective products for the treatment and prevention of topical infections including those caused by antibiotic-resistant bacterial strains, announced the publication of key data demonstrating that development of resistance to NovaBay’s lead Aganocide compound, NVC-422, is highly unlikely for a variety of infectious organisms, including methicillin-resistant S. aureus (commonly known as MRSA), compared to traditional antibiotics. Study results were published in the May 2012 issue of Antimicrobial Agents and Chemotherapy, the journal for the American Society for Microbiology.
NovaBay is developing NVC-422, a novel anti-infective with broad-spectrum bactericidal activity and novel mechanism of action to address the unmet medical needs in several large markets. Different topical formulations of NVC-422 are in mid-to-late-stage clinical development in ophthalmology, dermatology and urology.
“Despite worldwide efforts, the battle against antibiotic resistance continues. With microbial evolution outpacing human invention, there is a growing need for truly novel compounds,” commented Dr. Richard Odom, Sonoma Dermatology, Sonoma, Calif., and past president of the American Academy of Dermatology. “This is a seminal article for those in the industry of infectious diseases, as it confirms the potency of NVC-422 against potentially deadly bacteria, and shows the bacteria’s low likelihood to develop resistance to NVC-422. As a practicing dermatologist, I believe a new topical agent of this nature would be a welcomed addition to our treatment options, particularly in highly drug-resistant infections such as caused by MRSA.”
In the study, NVC-422 was tested for development of resistance in strains of E. coli, P. aeruginosa, and S. aureus, including MRSA. The study used a well-recognized serial passage model to determine if the bacteria are likely to develop resistance over time. Compared to antibiotics currently used today, NVC-422 was the only antimicrobial agent tested to which bacterial susceptibility remained unchanged for up to 50 passages, indicating that the bacteria did not become resistant. In fact, over the course of the entire study, there was no significant increase in the minimum inhibitory concentration2 (MIC) for NVC-422 against any of the organisms tested.
“Passage studies are important predictors for the development of drug resistance. Our Aganocide compounds kill bacteria by inactivating proteins on the bacterial cell surface, resulting in a low probability of resistance development,” explained Dr. Dmitri Debabov, senior author and Head of Microbiology and Cell Biology at NovaBay. “This study not only showcases NVC-422 as an antimicrobial agent that has a strong potential of being ‘immune’ to resistance, it also highlights the inadequacies of current antibiotics because bacteria can rapidly become resistant, especially when antibiotics are used at sub-lethal concentrations.”
In stark contrast to NVC-422, MICs for the broad-spectrum antibiotic comparator, ciprofloxacin, increased over 250-fold for E. coli and over 30-fold for both P. aeruginosa and S. aureus after 25 serial passages.
For highly drug-resistant MRSA, MICs for currently used topical antibiotics mupirocin, fusidic acid, and retapamulin increased 64-, 256-, and 16-fold, respectively, after 50 serial passages. Importantly, strains that developed resistance to these antibiotics were still killed by the same concentration of NVC-422 as killed the original susceptible strains, highlighting the potential benefit of this novel class of anti-infectives in fighting the spread of resistant pathogens.
“Our Aganocide compounds belong to a novel family of antimicrobial compounds with a mechanism of action that is not conducive to the emergence of resistance,” stated Dr. Ron Najafi, NovaBay’s Chairman and Chief Executive Officer. “The compounds are not cross-resistant with other known structural families, and to date, we have not selected or identified strains resistant to NVC-422, which has been the subject of several clinical and in vitro studies.”
Date: May 2, 2012
Source: NovaBay Pharmaceuticals Inc.
Filed Under: Drug Discovery