Nitric oxide plasma technology from US start-up Origin, Inc could hold the key to wound healing for patients suffering from chronic diabetic foot ulcers. Based on Nobel prize winning research, the privately-held company has developed a handheld, computer-guided system that generates NO from ambient room air within a defined plasma stream.
Diabetic foot ulcers (DFUs) continue to be one of the major health challenges associated with diabetes patients and a major cost burden to healthcare providers. According to a 2014 study published in Diabetes Care, care of DFUs adds an additional $9-12bn to healthcare costs for diabetics. The condition, which is often the result of sensory neuropathy, is the leading cause of non-traumatic lower extremity amputations in the US, with approximately 7-15% of diabetics developing foot ulcers each year and up to 15% requiring amputation.
One company hoping to address the challenge is US start-up, Origin, Inc which is pioneering a proprietary plasma solution for patients suffering from chronic DFUs. The New Jersey-based company is developing a device that produces and delivers therapeutic quantities of plasma-generated nitric oxide.
Nitric oxide (NO), a small radical formed from the amino acid L-arginine by three distinct isoforms of nitric oxide synthase, has been evidenced to play a key role in wound repair due to its functional influence on angiogenesis, inflammation, cell proliferation, matrix deposition and remodelling. The start-up aims to bring to market a handheld, computer-guided device that generates plasma NO from ambient room air within a defined plasma stream and delivers the NO directly to the target treatment area.
"The way the technology works is that at the point of delivering the therapy you use a high voltage electrical arc that is passed across a catalyst and a stream of ambient air," Betsy Hanna, Origin's chief operating officer tells Medtech Insight. "Air inside the room is pumped over the arc which then energizes the air stream and takes it to a highly energized plasma state. Because of the particular catalyst that is used, a plasma state is generated from the nitrogen and oxygen in the ambient air, generating a high therapeutic concentration of nitric oxide."
The company is kick-starting a US dose-ranging trial, GENESIS, to demonstrate the device's healing properties and optimize dose treatment for DFUs. The single-blinded, 27-week study will recruit up to 100 patients across 15 clinical sites in the US After a two-week run-in period, patients will then be randomized into one of four different dosing regimens or a standard of care treatment arm to assess efficacy and safety. Effectiveness will be measured by wound closure rate (in cm2 of epithelium coverage per week) and wound closure percentage (effectiveness measures for the study analysed through a maximum of 12 weeks of treatment). Safety will be measured by wound-related adverse events, which include adverse events of all causes that affect the wound.
"The objectives of this study are two-fold," explains Hanna. "Firstly, we are continuing to establish for the US FDA that there are no safety side effects to this therapy. The second thing we are doing with this study is we are looking to optimize the frequency and time of treatment for healing chronic DFUs. The study is designed with four different treatment arms to test multiple days a week and different treatment times to see if there is a healing rate response difference in any of those different frequency and time applications."
Origin Inc., founded under the name of Advanced Plasma Therapies, was established in 2010 to explore the broader area of plasma medicine. It was particularly interested in plasma's ability to deliver specific therapeutic molecules topically and the firm discovered a Russian plasma NO company that was using its technology for wound healing applications in Russia and Eastern Europe. The research behind the technology had won a Nobel prize and the technology's use in wound care was awarded the Russian Federation Prize for Science. In 2011, Origin's five founders secured an option to acquire the US patent for the technology and in 2014 began fundraising to expand development.
To date, Origin has raised in excess of $30m from private investors and from Woodford Investment Management, a leading healthcare fund based in Oxford, UK. At present, the company is raising additional funds to drive completion of this dose optimization study. If results prove to be positive, Origin aims to go through the US premarket approval process with the FDA.
As well as DFUs, Origin believes the technology could be used for multiple indications in wound care management, either as a replacement or in conjunction with other advanced therapies used for patients not responding to the current standard-of-care wound therapies.
Hanna says: "There is a huge unmet need in terms of healing of chronic ulcers but certainly with diabetic foot ulcers. We see this technology as something that can be used for wounds that are not healing after basic standard of care. Nitric oxide stimulates the body's natural healing mechanisms in place so we see this as something that can help accelerate and jump start healing where wounds otherwise are not repairing. The intent is to get that healing process going so you don't see a patient going down the path that ultimately leads in many cases to amputation."