According to a 2010 survey, 66% of Americans had never heard of the word ‘sepsis’, and of the remaining third who had, 35% had no idea what it meant. The result is shocking considering that sepsis is the leading cause of mortality in U.S. hospitals, with 750,000 patients and over 250,000 deaths each year. The most dangerous form of sepsis, i.e. severe sepsis and septic shock has a combined mortality rate of 30 to 35%.
Sepsis poses a healthcare crisis that is becoming pandemic in the U.S. and worldwide. The Global Sepsis Alliance defined sepsis last year for what it represents, i.e. a worldwide medical emergency and possibly the leading cause of death worldwide, which kills tens of millions every year.
Even though the situation is very serious indeed, there is still not one FDA-approved drug on the market today which can treat severe sepsis and septic shock. In late 2011, Eli Lilly withdrew Xigris from the U.S. market, due to efficacy and safety problems, which highlighted the urgent need for new efficient and cost-effective treatments. Another drug, Eritorin (Eisai) intended for the use of severe sepsis, failed the efficacy test in its phase III trial, whilst Agennix AG stopped its Phase II/III trial of talactoferrin in February 2012 because of safety issues.
Canadian and U.S. researchers are currently participating in EUPHRATES, a late-stage North American multi-center clinical study, which is evaluating whether a combination therapeutic/diagnostic (theranostic) can improve patient survival in those with severe sepsis and septic shock. EUPHRATES is the first study assessing a theranostic for the diagnosis and treatment of sepsis. It also differs from other studies insofar that it applies principles of personalized medicine to identify and treat a specific subgroup of the patient population that has the highest risk of mortality.
Earlier studies have demonstrated that elevated endotoxin levels in the blood, a condition known as endotoxemia, can be a potent trigger of the “sepsis cascade”, i.e. the physiological chain of events that may ultimately result in organ failure and death. About half of all patients with severe sepsis, which is around 125,000 patients, have endotoxemia.
The theranostic substance in the EUPHRATES study consists of Endotoxin Activity Assay (EAA™) and Toraymyxin™. EAA™ is an FDA-cleared rapid diagnostic that measures endotoxin levels in the blood, whilst Toraymyxin™ is a therapeutic hemoperfusion device that removes endotoxin from the bloodstream and is already approved in 18 countries and has safely treated over 80,000 patients. However, in the U.S., Toraymyxin is still an investigational device. JAMA published interim results of a Phase II study in 2009, which demonstrated that Toraymyxin, when added to conventional therapy, substantially reduced 28-day mortality in patients with severe sepsis and septic shock, unlike patients who only received conventional therapy. The trial was terminated early because of these positive results, and a Phase III pivotal multi-center study has been launched in the U.S. and Canada.
If the EUPHRATES trial should prove successful, the potential first effective treatment would mean a major breakthrough in an area of unmet medical need and it would change the way in which most patients are currently treated for sepsis.
Written By Petra Rattue