Broad Cytokine and Toxin Reduction
to Control Deadly Inflammation
CytoSorb® is the first specifically approved extracorporeal cytokine adsorber in the European Union, designed to reduce the “fuel to the fire” of deadly inflammation often seen in critically-ill patients in the intensive care unit (ICU) suffering from common but deadly illnesses such as sepsis and infection, influenza, COVID-19, trauma, burn injury, liver failure, acute respiratory distress syndrome, cytokine release syndrome in cancer immunotherapy, complications of surgery, and many others, as well as those undergoing complex open heart surgery. It has been used in more than 131,000 treatments to date and is distributed in 68 countries worldwide. Although CytoSorb is not yet approved in the U.S., CytoSorb was granted FDA Emergency Use Authorization in the U.S. for use in adult, critically ill COVID-19 patients with imminent or confirmed respiratory failure, and is commercially available for this indication.*
Specifically, CytoSorb is E.U. approved to reduce excessive cytokines, often called a “cytokine storm”, as well as to reduce bilirubin and myoglobin in clinical conditions such as liver disease and severe trauma, respectively, from the bloodstream. In doing so, CytoSorb targets the prevention or treatment of one of the most dreaded consequences of an uncontrolled, systemic inflammatory response: the failure of vital organs such as the brain, heart, kidneys and lungs. Multiple organ failure has no effective therapy other than supportive care today, accounting for nearly half of all deaths in the ICU, and remains one of modern medicine’s greatest and most costly unmet medical needs.
When Inflammation Becomes Toxic
Localized inflammation is a normal response to injury or infection, and helps to bring blood cells, oxygen and nutrients to the affected area to assist in the healing process. However, the body’s immune system frequently overreacts in response to life-threatening conditions such as sepsis and infection, trauma, burn injury, severe lung injury, liver failure, pancreatitis, influenza, cytokine release syndrome, and many others. This overreaction can lead to the production of a massive excess of inflammatory mediators, particularly cytokines, which is often called a “cytokine storm”. Cytokines are a class of more than one hundred different small proteins that normally help to stimulate and regulate the immune response to help the body cope with injury and infection and include the family of interleukins, interferons, tumor necrosis factor, and many others.
Cytokine storm is toxic to the body, driving severe generalized inflammation and a cascade of pathophysiologic changes in the body that cause cell death, organ failure and often death of the patient. Shock, respiratory failure, and kidney failure are common examples of organ failure in critically ill patients. Reduction of cytokine storm has the potential to limit this cascade of events, thereby helping to mitigate organ injury, while reducing the severity of illness, and helping patients to recover and survive. Until recently, there were no effective ways to reduce cytokine storm broadly.
CytoSorb® – Reducing the Fuel to the Fire of Inflammation
CytoSorb is approved in the European Union as an extracorporeal cytokine adsorber to reduce circulating cytokines in the bloodstream, and is broadly indicated for use in clinical situations where cytokines are elevated. In preliminary pre-clinical and/or clinical studies, CytoSorb has also demonstrated the ability to reduce bacterial toxins, free hemoglobin, bilirubin, myoglobin, activated complement, and a host of other inflammatory mediators in whole blood that are often associated with critical illnesses treated in the ICU. Because of this, CytoSorb represents a potentially important advance in the control of deadly inflammation in critically-ill patients and those undergoing complex cardiac surgery.
CytoSorb is compatible with most standard hemodialysis machines, continuous renal replacement therapy (CRRT) machines, heart-lung machines, most extracorporeal membrane oxygenation (ECMO) machines, and other blood pumps found in most hospitals. Using a standard hemodialysis machine, 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 over and over again. In a twenty-four hour period, a patient’s entire blood volume can be treated more than 70 times.
For more information on CytoSorb and its application in critically ill patients, please visit our product website at www.cytosorb.com
* The CytoSorb device has been authorized by FDA under an EUA for use in COVID-19+ patients. It has neither been cleared nor approved for the indication to treat patients with COVID-19 Infection.
CytoSorb and Cardiothoracic Surgery Applications
CytoSorb has been used in more than 10,000 open heart surgeries worldwide to date, installed into cardiopulmonary bypass, in a wide variety of procedures where cytokines are elevated and patients are often unstable. In 2020, CytoSorb also received E.U. approved to remove the anti-thrombotic drugs, ticagrelor and rivaroxaban, during emergent or urgent cardiothoracic surgery. If not removed, these drugs, also termed “blood thinners, can cause serious and potentially life-threatening perioperative bleeding in these patients.
In the United States, CytoSorb is not yet approved but is on a dual pathway for potential FDA approval. In 2020, CytoSorbents received U.S. FDA Breakthrough Designation for its technology to remove ticagrelor during urgent or emergent cardiothoracic surgery. The U.S. STAR-T (“Safe and Timely Antithrombotic Removal of Ticagrelor”) randomized, controlled, pivotal trial is expected to commence in Q3 2021, and if successful, is intended to support U.S. FDA marketing approval.
The REFRESH 2-AKI (REduction in FREe Hemoglobin to prevent AKI) pivotal RCT represents a second path to potential U.S. regulatory approval where CytoSorb is being used intraoperatively with cardiopulmonary bypass in high risk cardiac surgery patients to remove inflammatory toxins, such as free hemoglobin, activated complement, and cytokines, to prevent or reduce the severity of post-operative acute kidney injury (AKI). The development of even mild AKI is directly correlated to an increase in mortality up to 5 years after the surgery, and a risk of chronic kidney disease requiring hemodialysis. The trial is currently enrolling.
For more information on CytoSorb and its application in cardiothoracic surgery patients, please visit our product website at www.cytosorb.com
CytoSorb® in Cardiopulmonary Bypass (CPB) during Cardiac Surgery
- Approved in the E.U. to remove excess cytokines and anti-thrombotics
- Installs into CPB circuit easily and within minutes
- Utilizes blood flow generated by the CPB circuit, no need for another blood pump
- Blood in, blood out; No dialysate, ultra-filtrate to be concerned about
- High flow, low resistance and can accommodate high blood flow rates at least to 700 mL/min without hemolysis
- 7+ football fields of surface area vs. 1-3 square meters in membrane-based filters
- Compatible with systemic heparin anti-coagulation used during CPB
CytoSorb® + ECMO = A Novel Lung Rest Strategy
Extracorporeal membrane oxygenation (ECMO) therapy is a growing treatment modality used in ICUs around the world as a rescue therapy for patients with lung injury who fail mechanical ventilation. Like a heart-lung machine, ECMO takes blood out of the body, oxygenates it, and recirculates it back into the body, providing required gas exchange without the need for functional lungs. ECMO can help to rest the lungs and reduce the risk of ventilator-induced lung injury (VILI). However, it does not reduce cytokine storm and other circulating inflammatory mediators that can cause ongoing injury to the lungs. CytoSorb has been used in thousands of ECMO treatments as a means to reduce cytokine storm to help promote lung rest and healing, and has been used extensively with ECMO during the COVID-19 pandemic for this purpose.
CytoSorb® in Extracorporeal Membrane Oxygenation (ECMO)
- CytoSorb® can be integrated rapidly into ECMO in a bypass circuit
- CytoSorb® reduces circulating cytokines that can cause ongoing lung injury
- CytoSorb® + ECMO could potentially become useful as a therapeutic intervention for lung injury in the ICU
For more information on CytoSorb and its application with ECMO, please visit our product website at www.cytosorb.com
Liver Disease, Cytokine Release Syndrome, and Other Future Applications
One in 11 people worldwide have chronic liver disease from either alcoholism, viral hepatitis, or fatty liver (i.e. NASH). Many patients with advanced chronic liver disease will develop an acute exacerbation or decompensation (“acute-on-chronic”) of their disease, with associated inflammation and cytokine elevation, often requiring hospitalization. Also, many patients will present with acute hepatitis triggered by viral infection or alcohol. A range of symptoms, depending on the severity of illness include jaundice (high bilirubin), variceal hemorrhage, cognitive dysfunction and hepatic encephalopathy, ascites, coagulopathy, renal failure, liver failure, and others. The extracorporeal blood purification of liver toxins such as bilirubin has been used to help treat patients and is often called “liver dialysis”. Current liver dialysis therapies include MARS (Molecular Adsorbent Recirculation System; Baxter), Prometheus (Fresenius), SPAD (single pass albumin dialysis), and others. However, none of these therapies can remove cytokines, key elements in acute-on-chronic exacerbations and cases of acute hepatitis. In May 2018, the approved indications for use of CytoSorb in the E.U. were expanded to include the removal of bilirubin in liver disease. representing a potentially superior liver dialysis therapy, as it can remove both bilirubin and also cytokines.
Another application of CytoSorb® is to help control the deadly cytokine release syndrome (CRS) that occurs in many patients undergoing certain types of cancer immunotherapy. One such example is CAR T-Cell immunotherapy, one of the most promising new immunotherapy strategies to treat leukemias and lymphomas. Following chemotherapy pre-treatment and the administration of T-cells that have been modified to hunt and kill tumor cells, patients often develop a hyper-activation of the immune response, leading rapidly to a cytokine release syndrome (a form of cytokine storm) in up to 20% of patients, which can degenerate into organ failure and death in a number of cases. CytoSorb® was specifically designed to treat cytokine storm and has been used to help reverse this hyper-inflammation, with positive outcomes in a number of published case reports.
For more information on CytoSorb and its application in liver disease and cancer immunotherapy, please visit our product website at www.cytosorb.com
CytoSorb® Availability is Expanding Worldwide
CytoSorb® Availability is Expanding Worldwide CytoSorb® is available in 68 countries worldwide under European CE Mark approval including the majority of the European Union and countries outside the E.U. such as India, Russia, South Korea, Mexico, Brazil, the Middle East, Israel, Australia, Vietnam and others. The total addressable market for CytoSorb® in critical care applications (such as sepsis, burn injury, trauma, ARDS, pancreatitis and other diseases) and cardiac surgery is estimated at more than $20 billion worldwide.
CytoSorb®: State of the Art Technology
- Highly Adsorbent: Massive capacity with more than 7 US football or 5 international soccer fields (>40,000 m2) of surface area per CytoSorb cartridge to bind toxic materials
- Biocompatible: Porous polymer beads are ISO 10993 certified. Biocompatible, hemocompatible, non-genotoxic, non-cytotoxic, with no acute sensitivity or complement activation.
- Good Safety Profile: 131,000+ human treatments, well-tolerated. No significant change in blood chemistries
- Pure: No residual organics, no leachables, meets USP particulate standards for large parenteral injections.
- Robust: High flow, low resistance cartridge capable of treating whole blood or plasma with flow rates of 100-400 mL/min using a dialysis or CRRT machine and up to 700 mL/min using a heart-lung machine without hemolysis helpful in countering ongoing cytokine production.
- Stable with Long Shelf Life: Solid state chemistry with no cells, biologics or other perishable materials, gamma sterilized with 3-year shelf life at room temperature
- Easy to use: Blood in, blood out. No dialysate or replacement fluid needed.
- “Plug and Play”: Compatible with a wide range of extracorporeal blood pumps