What is CytoSorbents potential for success in sepsis? Print E-mail
By Patrick Crutcher   
Sunday, 06 March 2011 01:58

best penny stock picksWith Cytosorbents Inc.(OTC: CTSO) close to completing their severe sepsis trial, it's natural to consider whether or not their device has the potential to be clinically and/or statistically significant.

Currently, we have little robust clinical data from CTSO, so it's definitely a potential concern going into the top-line results. If we had any additional clinical data that we can observe, even if from a similar device, that would be actionable information. Interested investors should also keep an eye on the ClinicalTrials.gov site(link).

As we know, CytoSorbents is developing CytoSorb for the treatment of severe sepsis. CytoSorb is a hemoperfusion device(think, blood filter) that utilizes highly porous polymer beads designed remove certain proinflammatory and anti-inflammatory cytokines(eg. TNF-α, IL-1b, IL-10) from blood and physiologic fluids without reducing immune function. They currently running a 100 patient study in the EU, data from which they will use to support an application for CE Mark approval in the EU. This is randomized, placebo-controlled study comparing the standard of care(SOC) therapy versus SOC plus CytoSorb in the treatment of patients with severe infection and sepsis in the setting of acute respiratory distress syndrome(ARDS) or acute lung injury (ALI).

 It's important to consider whether Cytosorbents device has a supportive scientific rationale. First, there is a considerable amount of research supporting high levels of cytokines in association with poor clinical outcomes, pulmonary function and other vital indicators. One of their lead medical advisors is Dr. John Kellum, M.D., Associate Professor of Critical Care Medicine and Anesthesiology, University of Pittsburgh Medical Center. He has led numerous studies in severe sepsis thru work with The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory at the University of Pittsburgh, specifically into the role of cytokine levels and outcomes in severe sepsis. He was also a part of Lilly's Xigris development and clinical trials, the only approved treatment option for sepsis; he also worked on Sanofi's failed sepsis drug, Eritoran.

In a recent large, retrospective study (n=1886)[1], Kellum et. al found that elevated cytokine levels and 90-day mortality were statistically significant in patients with severe sepsis associated with community-acquired pneumonia(CAP). They've also done investigative work into survival of patients discharged following treatment for CAP, which prospectively showed that "many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death." There are several other studies which have supported cytokines role in sepsis. Through UPitt, Dr. Kellum recently received $948K from the US Dept. of Health and Human Services, to evaluate whether Cytosorb can help improve the quality of organs in brain-dead donors before they are removed for transplantation. It will evaluate the use of CytoSorb in donors to determine its ability to absorb cytokines before they invade tissue and impair organ function. He is also interested in the devices role in acute kidney injury. Much of Kellum's recent work in the sepsis community has focused on bringing the attention to the role of cytokines and their association with increased mortality.

We had the chance to speak briefly with Dr. Kellum. There were several things in particular that he said to consider. "The primary goal of the study is to show that CytoSorb can reduce levels of IL-6. Although the EU trials were not powered to demonstrate statistical significance for survival, it would be great to see positive trends in the 28-day all cause mortality and organ failure scores." He also said that pending the EU data, he would likely be involved in running a larger trial in the US. 

Additionally, we found that the approach CytoSorbents is making with CytoSorb has been done(to some extent) in Japan as recently as 2010. In several recent articles in Contributions to Nephrology, clinicians in Japan outlined results from a study done in 51 patients with a diagnosis of ARDS complicated by renal failure and without prior steroid therapy, wherein they were investigating the use of a device that utilizes a cytokine-adsorbing hemofilter with a membrane made of polymethylmethacrylate (referred to as PMMA-CHDF). In their study[4], the device showed a nearly 86% increase in 28-day all cause survival in sepsis patients with ARDS. Although Cytosorbents' device is different, it is the same approach: filter out the cytokines to improve the clinical outcome. With results like that, CytoSorb could be a clinically meaningful product in the marketplace. 

Admittedly, the trial has been to slow to complete enrollment. The last update in regards to trial enrollment was in November 2010, where they indicated that the trial had enrolled 90 of 100. One cause for slow enrollment is likely do to Cytosorbents limited financial resources. They recently raised $1.25 million, since they were very low on cash of approximately $500-750k. With positive results, Cytosorbents should seek a larger commercial partner in exchange for an upfront payment and backend royalties; they are in need of non-dilutive financing in order to remain viable.

Given the scientific rationale and clinical data from similar devices, we are cautiously optimistic for positive results from their trial. Investors should consider their risk-reward profile here and position themselves accordingly; it is an OTC stock with limited finances. CE Mark approval isn't that difficult, but getting reimbursement is a different story. If their device can effectively demonstrate efficacy in severe sepsis, CytoSorb could unlock a large, mostly untapped market that is need of better treatment options.

Disclosure: Long CTSO (small position)

Cytosorbents investors anxious for European data - http://biomedreports.com/2011012862985/cytosorbents-investors-anxious-for-european-data.html

The Wall Street Transcript Interview with Dr. Philip Chan, CEO of CytoSorbernts, Inc.(PDF) - http://bit.ly/gpxyIi

 References for work done at the University of Pittsburgh

[1] "Fatal sepsis in hospitalized pneumonia patients is most likely to occur in the presence of high levels of certain proinflammatory and anti-inflammatory cytokines, investigators here found." http://bit.ly/dGciNv

[2] "Inflammatory Markers at Hospital Discharge Predict Subsequent Mortality after Pneumonia and Sepsis" http://bit.ly/g8Mieu

[3] "Clinical review: Blood purification for sepsis" (2011) http://1.usa.gov/gwkTal

References for work done in Japan

[4] "Efficacy of continuous hemodiafiltration with a cytokine-adsorbing hemofilter in the treatment of acute respiratory distress syndrome." http://1.usa.gov/hwtAF7

[5] "Treatment of severe sepsis and septic shock by CHDF using a PMMA membrane hemofilter as a cytokine modulator." http://1.usa.gov/e99Iou

[6] "Non-renal indications for continuous renal replacement therapy: current status in Japan." http://1.usa.gov/gGf5Pb

[7] "Cytokine adsorbing columns." http://1.usa.gov/fJjXsh

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