The current public health war against bacterial infections is rapidly approaching a critical stage, in which bacterial resistance to antibiotics becomes widespread and our reservoirs of available antibiotics and viable therapeutics are depleted. During the past 60 years, the rise in the frequency of resistance, particularly to multiple drugs, has thwarted the treatment of patients in the hospital and the community. According to Rabih Darouiche, MD, of Baylor College of Medicine, microbial resistance is emerging faster than we are replacing our armamentarium of antimicrobial agents.
Darouiche, in collaboration with the product development team from NovaBay Pharmaceuticals, recently published a monograph on NovaBays lead Aganocide® NVC-422 in the journal Drugs of the Future, a leading interdisciplinary biomedical research journal publishing peer-reviewed articles on emerging topics in medicine, pharmacology, biology and chemistry.
The Aganocide® compounds are novel, synthetic N-chlorinated antimicrobial molecules specifically designed and developed to mimic the bodys natural defense against infection. The topical Aganocide compounds maintain biological activities while demonstrating improved stability over the naturally occurring N-chlorinated antimicrobial molecules. In preclinical testing, NovaBays Aganocide compounds have been shown to be highly effective against bacteria, including some multi-drug resistant strains (such as MRSA), viruses and fungi. NovaBays Aganocide compounds have the potential to deliver the same or better efficacy than antibiotics, and to address the growing problem of antibiotic resistance by employing a novel mechanism of action.
The monograph introduces NVC-422 as a first-in-class synthetic stable chlorotaurine exhibiting a broad spectrum of activity against Gram-positive and Gram-negative pathogens, without the potential for developing drug resistance. The monograph highlights the Phase II clinical studies in impetigo, catheter-associated urinary tract infections, urinary catheter blockage and encrustation, and adenoviral conjunctivitis as well as the preclinical safety and background. NVC-422 has been shown to be well-tolerated, and its mechanism of action, time-kill and lack of observed drug resistance uniquely differentiates it from traditional antibiotic agents.
NovaBay is focusing the Aganocide technology on four distinct therapeutic areas: dermatology, ophthalmology, urology and hospital infections. In dermatology, the focus is on developing an NVC-422 gel formulation for the highly contagious skin infection of impetigo. In ophthalmology, the goal is to develop an eye drop for viral conjunctivitis. In urology, NVC-422 aims to reduce the incidence of urinary catheter blockage and encrustation (UCBE) and the potential for urinary tract infections with an irrigation solution containing NVC-422. In hospital infection, NovaBay is targeting chronic non-healing wounds, such as pressure, venous stasis and diabetic ulcers, with its proprietary anti-infective solution, NeutroPhase, which has received two 510(k) clearances from the Food and Drug Administration.
As a consequence of microbial resistance, there is an evolving unmet medical need for novel antimicrobial agents that are effective against resistant pathogens and that carry a low potential for the development of drug resistance, says one of the papers co-authors, Ron Najafi, CEO of NovaBay. Efforts focusing on the screening of large combinatorial chemical libraries for promising antimicrobial compounds have been rather disappointing. We have demonstrated that Aganocide® NVC-422 is well tolerated, with no safety issues. The broad-spectrum activity, low probability of the development of drug resistance and good clinical tolerability may make NVC-422 an effective alternative to known antimicrobial compounds for the treatment of non-systemic infections.