The U.S. Food and Drug Administration (FDA) has agreed to designate NA Medical LLC's CeraShield endotracheal tube as a breakthrough device pursuant to the recently enacted 21st Century Cures Act. A breakthrough device is a product that may prevent a life-threatening or irreversibly debilitating disease or condition.  
 
Each year more than 4 million Americans hospitalized in intensive care units (ICUs) require the use of an endotracheal tube attached to a ventilator to help them breathe. 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 can 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, Mass., and New York, N.Y. N8 also supplied the 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 U.S. 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 in Provo, Utah. There are more than 40 peer-reviewed journal articles on the ceragenin technology, and the technology is protected by issued patents through 2033. Brigham Young has licensed the ceragenin technology to N8 Medical for certain fields of use, including application to medical devices.
 
The N8 Medical’s CeraShield Endotracheal Tube 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 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.

“Among the potential benefits of the technology are that it may reduce mortality, 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,” said Carl Genberg, CEO of N8 Medical LLC.  
 
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 percent 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 has been the subject of a 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 anti-fungal 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 micrograms/ml for all strains, and some strains with MICs of 0.5 micrograms/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.
 
Ronald Bracken, N8 Medical’s president and chief operating officer, a medical device industry veteran and formerly vice president of research and development for C.R. Bard, added, “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.”
 
“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,” said David J. Richards, N8 Medical's board chairman. “We now look forward to working closely with the FDA to try to reduce the time to get devices to the patients that need them, while still maintaining the high standards of safety, efficacy and scientific validity required by the program.”
 
The modern age of antibiotic therapy began with the discovery and introduction of penicillin. Penicillin in was rightly regarded as a “wonder drug” or “magic bullet” as patients at death’s door in hospitals were cured of their infections and sent home to resume normal lives. However, widespread use of the drug led to the development of new strains of bacteria resistant to penicillin. A modified form of penicillin—methicillin—was thereafter developed, and similarly widespread use of that drug led to methicillin led to highly virulent methicillin-resistant staph aureus (MRSA).  Widespread use of other antibiotics has also led to the emergence of deadly multidrug-resistant strains. The World Health Organization and other health agencies have repeatedly warned that humanity may be entering a “post-antibiotic” age and could be at the end of the modern era of antibiotic therapy due to the lack of development of new effective antibiotics.
 
Prior to the introduction of modern antibiotics, infections were a leading cause of death in the United States and elsewhere. The lack of antibiotic therapy for newly-emerging antibiotic resistant strains is posing a serious threat to global health. According to a study commissioned by David Cameron, the United Kingdom’s former prime minister, if urgent action is not taken to develop new countermeasures, the annual worldwide death rate may reach 10 million persons per year by 2050, with a loss of global economic production between $100 trillion by 2050. N8 Medical believes that its CeraShield coating technology is poised and ideally-suited to address this major worldwide health concern. 

“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 and ventilator associated tracheobronchitis, which may lead to poor clinical outcomes, including death," said Professor Michael Niederman, chairman of N8 Medical’s Scientific Advisory Board and associate division chief, clinical director of pulmonary and critical care at New York Presbyterian /Weill Cornell Medical Center. "Here 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.”
 
In the United States, the CeraShield endotracheal tube is limited by law to investigational use only.

N8 Medical LLC is a privately-held company developing novel solutions for the prevention of hospital-acquired infections from multidrug-resistant pathogens.