CytoSorb® is a potentially breakthrough critical care immunotherapy that attempts to address one of the most challenging unmet medical needs in medicine…the ability to prevent or mitigate multiple organ failure - the leading cause of death in the intensive care unit (ICU) from any cause.
In response to life-threatening conditions such as sepsis and infection, trauma, serious burn injuries, severe lung injury, and pancreatitis, the body frequently overreacts and produces a massive excess of cytokines, or “cytokine storm”. Cytokines normally help the body cope with injury, but at these levels, cytokine storm is toxic to the body, driving severe inflammation and a cascade of pathophysiologic changes in the body that cause cell damage, organ failure and often death. It follows that reduction of cytokine storm may limit this cascade of events, thereby reducing the severity of illness, and helping patients recover and survive. Until recently, however, there were no effective ways to reduce cytokine storm broadly.
CytoSorb® is a first-in-class extracorporeal cytokine adsorber, now approved in the European Union, and broadly indicated for use in any clinical situation where cytokines are elevated. It is compatible with standard hemodialysis machines and blood pumps found in most hospitals. Blood is pumped out of the body, through the CytoSorb® cartridge that contains the company’s proprietary blood compatible porous polymer beads, and the “purified” blood is recirculated back to the patient. In a twenty-four hour period, a patient's entire blood volume can be treated approximately 70 times.
CytoSorb® is clinically proven to reduce cytokines in the company's multi-center, randomized, controlled European Sepsis Trial conducted in Germany. More than 9,000 human treatments have been administered safely. Early data suggests that CytoSorb® can reduce organ injury and improve survival in patients at high risk of cytokine injury, particularly those patients with very high cytokine levels, and patients older than age 65. The company plans to conduct larger scale randomized controlled studies in the future to confirm these preliminary data.
CytoSorb® has now been used successfully in many conditions where deadly inflammation can lead to organ injury and failure. We are seeing strong interest in the following clinical applications:
There are hundreds of opinion leaders in Germany, Austria, and Switzerland (our direct sales territories) and elsewhere in the world who are supporting CytoSorb® in clinical practice or clinical studies. More than 50 investigator-initiated studies in a diverse set of applications are being planned, with many already enrolling patients. In the United States, the U.S. Air Force is funding a 30-patient, FDA-approved randomized controlled human trauma pilot study.
As these other independent studies progress, CytoSorbents collaborates with Dr. John Kellum at the University of Pittsburgh Medical Center, and is sponsoring clinical studies in the area of severe sepsis and septic shock, the result of an overzealous immune response to a severe infection such as pneumonia or a ruptured appendix. Severe sepsis and septic shock are collectively a top ten cause of death worldwide, afflicting approximately 27 million people annually, killing approximately 1 in 3 patients despite the best medical care. CytoSorbents is conducting clinical trials in Europe and currently has an FDA-approved IDE application to run a small sepsis trial in the U.S..
Because of the versatility of CytoSorb®, there are many other potential applications of the technology outside of critical care medicine as well. In particular, CytoSorb® has been used intraoperatively in more than 1,000 open heart surgeries (e.g. coronary artery bypass graft surgery, valve replacement, congenital defect repair, aortic reconstruction, etc), where the heart must be stopped in order to operate on it, while the blood is pumped outside of the body by a heart-lung machine that oxygenates the blood and pumps it back to the rest of the body.
This procedure can result in the production of inflammatory mediators such as activated complement and cytokines, as well as hemolysis and the release of free hemoglobin into the blood. Free hemoglobin is generated during open heart surgery due to hemolysis and blood administration, and increases proportionately with the length of the procedure. For this reason, concentrations of free hemoglobin in complex cardiac surgery cases (which typically take 2-6 hours to complete) are typically very high. Levels of free hemoglobin are toxic, causing oxygen radical formation and direct injury to blood vessels, while vigorously scavenging nitric oxide, a potent vasodilator, which results in decreased blood flow to vital organs. All of these factors can result in inflammation and post-operative complications such as failure to wean from mechanical ventilation, kidney failure, hemodynamic instability, intestinal injury, and cognitive dysfunction. CytoSorbents is currently enrolling its U.S. 40 patient, eight center, randomized controlled REFRESH I (REduction in FREe Hemoglobin) cardiac surgery safety and feasibility study with or without using CytoSorb® intra-operatively during complex cardiac surgery. The primary endpoints of REFRESH I are safety and removal of plasma free hemoglobin. The trial is expected to be completed by mid-2016. If successful, CytoSorbents plans to pursue REFRESH II, a pivotal trial designed to obtain U.S. regulatory approval. There are more than 1 million open heart surgeries each year in the U.S. and E.U. combined, with an addressable market of more than $1 billion for CytoSorb®.
Another application is in cancer immunotherapy. CytoSorb® was specifically designed to treat "cytokine release syndrome (CRS)" or cytokine storm. We believe that it can be used as a rescue therapy, when patients develop uncontrolled CRS in activated T-cell or CAR T-cell cancer immunotherapy. Cancer cachexia is another potential opportunity. Cancer cachexia is a wasting condition that occurs in most cancers that leads to rapid uncontrolled weight loss, anorexia, and physical debilitation. Patients lose the physical reserve needed to tolerate treatment and fight the cancer. Because CytoSorb® can remove a broad range of cytokines and other inflammatory mediators that drive cancer cachexia, it may be very helpful in this condition. CytoSorbents is exploring this application, as well as the use of CytoSorb® as a primary cancer immunotherapy to kickstart the immune system to attack cancer, with researchers at the University of Pennsylvania School of Veterinary Medicine.
CytoSorb® is now being distributed in 32 countries worldwide, including many in the European Union such as Germany, the United Kingdom, France, Italy, Netherlands, Denmark, Sweden, Norway, Sweden, Poland, and Romania, as well as in other parts of the world including India, Russia, Turkey, Israel, Australia, Vietnam, the Middle East, and others. The total addressable market for CytoSorb® in critical care applications such as sepsis, burn injury, trauma, ARDS, pancreatitis and other diseases is estimated at more than $20 Billion worldwide.
For more information, please visit the CytoSorb® Website