N8 Medical, LLC, a privately held medical device company developing novel solutions for the prevention of hospital-acquired infections from multidrug-resistant pathogens, has announced that FDA has approved the company’s request to designate its CeraShield™ endotracheal tube as a “breakthrough device” pursuant to the recently enacted 21st Century Cures Act. A "breakthrough device" is one that may prevent a life-threatening or irreversibly debilitating disease or condition.
According to N8, each year over 4 million Americans who are hospitalized in intensive care units require the use of an endotracheal tube attached to a ventilator to assist in breathing. Bacteria and fungi quickly grow on these tubes and may lead to potentially deadly respiratory infections and other severe complications. N8 supported its filing with FDA with recent data from the U.S. Centers for Disease Control and Prevention (CDC) showing that the antimicrobial compound in the CeraShield endotracheal tube was able to inhibit growth of all 100 strains of Candida auris — an emerging highly lethal fungal infection. While Candida auris infections have been found overseas they have only recently been found in U.S. hospitals with recent outbreaks in Boston and New York City. N8 also supplied FDA with peer reviewed published data showing efficacy against multidrug-resistant bacterial strains such as colistin-resistant Pseudomonas and Acinetobacter. Colistin is regarded as the antibiotic of last resort.
The 21st Century Cures Act enables companies to use a combination of premarket and postmarket approval studies to meet the requirements for a faster pathway toward approval. This significantly expedites access for US patients and their physicians to innovative medical devices. The statute was enacted in January 2017 for medical devices that demonstrate the potential to address unmet medical needs for life-threatening or irreversibly debilitating diseases or conditions, such as ventilator associated pneumonia and ventilator associated tracheobronchitis as well as other respiratory infections.
Ceragenins are mimics of molecules found within the human body’s own innate immune system, and were invented by Dr. Paul B. Savage, The Reed Izatt Professor of Chemistry and Biochemistry at Brigham Young University (Provo, UT). There are over 40 peer reviewed journal articles on the ceragenin technology, and the technology is protected by issued patents through 2033. BYU has licensed the ceragenin technology to N8 Medical for certain fields of use, including application to medical devices.
N8 Medical’s CeraShield is a specially modified endotracheal tube that has been coated with a proprietary ceragenin compound formulation designed to prevent bacterial and fungal growth on the tube’s surfaces. Patients who require mechanical ventilation in the Intensive Care Unit (ICU) are intubated with endotracheal tubes to provide oxygen to the patient’s lungs to assist the patients’ breathing. Within hours of intubation, bacteria and fungi may start to grow on the tube and form microbial aggregations known as biofilms. Biofilms consist of millions of bacteria and/or fungi and are almost impossible to eradicate through use of ordinary antibiotics.
Once a mature biofilm forms on an endotracheal tube, fragments may break apart and migrate to the lower respiratory tract causing difficult to treat, potentially lethal respiratory infections. Such infections are called nosocomial or hospital-acquired infections. Nosocomial infections associated with the use of endotracheal tubes are among the most common and most deadly of nosocomial infections. According to the U.S. Department of Health and Human Services (HHS), nosocomial infections claim the lives of nearly 100,000 Americans each year and add billions to the annual healthcare expenditures in the United States and globally. Approximately 70% of such nosocomial infections are believed to be related to the use of indwelling medical devices. Indwelling devices provide a “protected” breeding ground for bacteria and fungi that can lead to these life-threatening infections. Neonates, the elderly and immune compromised patients are at highest risk for such infections.
Particularly concerning is the emergence of multidrug-resistant pathogens, such as colistin-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, as well as the recently identified highly lethal fungus Candida auris. Candida auris was the subject of a U.S. Centers for Disease Control and Prevention (CDC) nationwide alert in June 2016 to healthcare institutions. CDC has recently tested CSA-131, the ceragenin in the CeraShield endotracheal tube, against CDC’s collection of 100 clinical isolates of Candida auris from around the world and representing four separate genetic clusters. Many of these isolates are highly resistant to fluconazole, a potent antifungal agent, and some are resistant to all commercially available antifungals. The CDC testing found that CSA-131 was active against all 100 strains of Candida auris with a maximum minimum inhibitory concentration (MIC) of 1 µg/ml for all strains, and some strains with MICs of 0.5µg/ml.
The CeraShield medical device coating technology is applicable to a broad range of medical devices commonly colonized with pathogenic bacteria and fungi, including urology, vascular access, cardiology, orthopedics, and ear vents, as well as other respiratory devices such as tracheostomy tubes as these devices may also be colonized with pathogenic bacteria and fungi.
N8 Medical holds a license to develop and commercialize ceragenins and welcomes collaborations and is interested in commercializing medical devices independently and in collaboration with other medical device aligned companies and organizations to develop best-in-class antimicrobial medical devices designed to reduce the morbidity and, mortality, and high costs and use of resources associated with hospital-acquired infections worldwide.
“Among the potential benefits of the technology are that it may reduce mortality and cost of care and improve clinical outcomes for ICU patients requiring mechanical ventilation, as well as slow or prevent the development of new antimicrobial resistant bacterial and fungal strains,” says Carl Genberg, chief executive officer of N8. Ronald Bracken, N8 Medical’s president and chief operating officer, says, “As someone who has developed and brought to market antimicrobial medical devices for over 20 years, I believe that the CeraShield technology is unparalleled in its broad spectrum antimicrobial, antifungal and anti-inflammatory activity, and I look forward to working with FDA to expedite the approval of this truly breakthrough device.” Bracken is formerly vice president of research and development for C.R. Bard.
“The breakthrough designation is an incredible opportunity to accelerate the path to approval in the United States, and we are honored to have been chosen to be among the small handful of devices that have met the FDA’s requirements for this designation,” says David J. Richards, chairman of the board of N8. “We now look forward to working closely with the FDA to try to reduce the time to get innovative devices to the patients that need them, while still maintaining the high standards of safety, efficacy, and scientific validity required by the program.”
Professor Michael Niederman, chairman of N8’s scientific advisory board and associate division chief, clinical director, Pulmonary and Critical Care, New York Presbyterian/Weill Cornell Medical Center, says, “In clinical practice, we regularly observe that despite high levels of antibiotic use, some mechanically ventilated patients in the ICU still go on to develop complications such as ventilator associated pneumonia (VAP) and ventilator associated tracheobronchitis (VAT), which may lead to poor clinical outcomes, including death. There is a great need to find new approaches to protect and treat such patients that will reduce the need for systemic antibiotic therapy while improving patient outcomes.”
NOTE: In the United States, the CeraShield™ endotracheal tube is limited by law to investigational use only.
For more information on efforts to address antimicrobial resistance, read "Tackling Drug-Resistance Infections Globally."
