Sepsis is a huge problem, costing billions of dollars and hundreds of thousands of lives a year in the US alone. A Toronto, Canada-based startup Spectral Diagnostics Inc. is developing a promising technology to decrease morbidity and mortality of patients with sepsis. The company’s proprietary technology is integrated into Toraymyxin, a hemoperfusion adsorption column which is highly effective in removing circulating endotoxin from the bloodstream. Furthermore, Spectral Diagnostics has also developed the Endotoxin Activity Assay (EAA) – the only FDA cleared, CE marked rapid diagnostic for endotoxemia. According to a company representative, in 2009 interim results of a Phase II study were published in JAMA demonstrating that “Toraymyxin, when added to conventional therapy, significantly reduced 28-day mortality in patients with severe sepsis and septic shock, compared to patients only receiving conventional therapy. Due to these positive results, that trial was terminated early and a Phase III pivotal multicenter study has been launched in the U.S. and Canada.” To find out more about this technology and its future, we had a chance to conduct an interview with Dr. Paul Walker, President and CEO of Spectral Diagnostics.
Dr. Jan Sinnige, Medgadget: Spectral Diagnostics recently started a phase three randomized controlled trial on Polymyxin B Hemoperfusion. What are the expectations according to the phase two results?
Dr. Paul Walker: The Polymyxin column has been safely treating patients since 1994 in Japan and has been the subject of nearly 60 clinical papers. The most similar trial to our ongoing Phase III EUPHRATES trial is EUPHAS, a randomized clinical study that was published in JAMA in 2009. In this trial, mortality was reduced from 53 percent to 32 percent. Given the positive results of EUPHAS, the FDA allowed us to move directly to a pivotal trial and the Meta analysis of many of the previous Polymyxin trials, which showed a similarly large reduction in mortality, was also used to plan for this pivotal trial. For the EUPHRATES trial, we predict a 43 percent relative reduction in the overall mortality in patients treated with Polymyxin.
Medgadget: Can the EAA Endotoxin Activity Assay be used to screen for early signs of sepsis and endotoxemia in intensive care units in the future?
Dr. Walker: The EAA is best used to answer the question, “is endotoxin playing a role in this patient’s disease?” Very few screening tests are useful in the ICU setting. The primary use of the EAA is to direct a specific treatment modality for a patient who is at high risk for death and also most likely to respond to that treatment.
Medgadget: Endotoxin activates blood clotting cascades. Are there any risks using this device with Heparin in severely ill patients?
Dr. Walker: Some patients who are auto anti-coagulated due to their disease do not require additional heparin. Most patients have a small loading dose then a short term infusion during the hemoperfusion run. The incidence of bleeding with the use of this column is extremely small, as has been shown in the 100,000 patients that have been safely treated.
Medgadget: Do you think that in the future, Spectral Diagnostics technology will be able to control or intervene in the reactive cytokine responses towards endotoxins?
Dr. Walker: There is published evidence that shows when the endotoxin is removed from the bloodstream, cytokine production decreases significantly. However, at this point, no studies have shown that reducing cytokines alone has a direct effect on mortality rate. Endotoxin directly effects many cells and especially contributes to myocardial depression, so removing endotoxin has many potential therapeutic effects.
Medgadget: When can we expect the trial results and when do you expect your technology on the market?
Dr. Walker: We are currently increasing the number of clinical sites and are expecting our first interim analysis in the first quarter of next year. We will have a better understanding of the timeline following that analysis.