ExThera Medical Corporation To Begin CE Mark Study in Germany

Berkeley, Calif.-based ExThera Medical Corporation, which makes broad-spectrum, dialysis-like devices to treat bloodstream infections, has received approval of its CE mark clinical trial protocol from Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the German Competent Authority. This approval, together with approval of the Ethics Committee of Hannover Medical School (also received), allows the company to begin its CE mark study in Hannover immediately. In this study, the company’s Seraph Microbind affinity blood filter will be used to treat dialysis patients who have Staphylococcus aureus and MRSA bloodstream infections. ExThera conducted a Clinical Site Initiation Meeting at Hannover in November and is awaiting enrollment of its first patient.

S. aureus and drug-resistant MRSA are the most common causes of infection in patients undergoing routine dialysis for kidney failure, and bloodstream infections are the second-most-common cause of death in end-stage renal disease patients because these infections can cause septic shock with multiple organ failure. Initially Seraph will be used for early treatment of bloodstream infections to prevent severe sepsis and reduce or eliminate ICU stays. Future clinical studies will concentrate on selected patients whose bloodstream infections have already progressed to severe sepsis or septic shock.

“Certain bloodstream infections have a mortality rate as high as 50 percent due to the lack of effective antibiotics. With fewer anti-infective drugs being developed, and the continuing emergence of drug- resistant pathogens, clinicians need new tools to fight bloodstream infections,” said Bob Ward, CEO of ExThera Medical.

ExThera Medical was the first to report the removal of bacteria from whole blood using a device instead of a drug. Early bench testing, and recent preclinical in vivo studies, have demonstrated that large amounts of MRSA are safely removed from blood as it passes through the Seraph device. ExThera has also published confirmation of Seraph’s ability to remove 99.9 percent of two Carbapenem-Resistant Enterobacteriaceae (‘CRE Superbugs’)—E. coli and Klebsiella pneumoniae—from blood after only brief contact with the Seraph adsorption media. Study results are published in the online journal PLOS ONE. In fact, Seraph may remove more than 60 different disease-causing bacteria, viruses and toxins, reported to bind to heparan sulfate and heparin, Seraph’s primary ligand.

Every year there are 1.8 million new cases of bloodstream infection in the U.S. and Europe, causing patients serious complications and imposing a high cost burden on health care systems. Not all are drug-resistant. However, an outbreak of CRE infections of unknown origin even occurred in the National Institutes of Health Hospital in Bethesda, and was the subject of the Frontline documentary, “Hunting the Nightmare Bacteria.”

Since 2008, privately funded ExThera Medical has been developing Seraph, which is now being manufactured under ISO 13485 Quality System. It enters clinical trials as a totally unique broad-spectrum ‘hemoperfusion device’. Seraph has demonstrated its ability to bind and remove a long list of disease-causing agents from whole blood, including viruses, bacteria, fungi and inflammatory cytokines. Unlike other devices still in early-stage development, Seraph is easily manufactured in large quantities from readily available raw materials.

According to Dr. Keith McCrea, CTO of ExThera, “Since its inception ExThera’s mission has been to offer simple, device-based therapies for rapid treatment of bloodstream infections—including those caused by pathogens for which there are no effective therapeutic drugs. We are very pleased to make our device available to dialysis patients who are highly susceptible to bloodstream infections via their blood access catheters. Our preclinical testing has demonstrated that Seraph can be used during dialysis without negatively affecting the blood. We have also determined that Seraph acts very quickly to reduce the level of blood-borne pathogens, and has a binding capacity that greatly exceeds the entire bloodstream concentration of pathogens in bacteremic patients.”

Seraph uses a biomimetic adsorption media that includes (chemically bound) heparin adsorbent materials in a simple, flow-through cartridge. The well-known anti-thrombogenic property of immobilized heparin also contributes to the safety of Seraph’s blood-contacting surface.
In addition to the potential to treat bacterial and viral infections for the prevention of sepsis, Seraph is a flexible platform that may be configured with optional supplemental adsorbents to deal with future weaponized, or naturally evolved, pathogens.