According to experts, severe sepsis is a life-threatening condition which can affect anyone, and most often develops in patients with pneumonia, trauma, surgery, burns or cancer. Over 18 million cases of severe sepsis occur each year – that’s equivalent to the entire population of Denmark, Finland, Ireland and Norway added together. In the U.S., it kills more people than either heart attacks, strokes or any single type of cancer.
The number of severe sepsis cases is grows at a rate of 1.5% per year, due mainly to the growing use of invasive procedures and increasing numbers of elderly and high-risk individuals such as cancer and HIV patients. Older people are at increased risk of sepsis as they are more prone to infections due to ageing, co-morbidities, use of invasive surgical techniques and other problems.
Yes, Sepsis is a major challenge in medicine and according to various publications, massive resources have been invested in developing and evaluating potential therapies, and considerable effort has been undertaken to understand the systemic inflammation and multiple-system organ failure characteristics of severe sepsis.
Three years ago, I nearly died when my blood became infected after a severe bout with diverticulitis. I suddenly fell very ill and ended up in the hospital for nearly three weeks as doctors fought, first to calm the severe infection that threatened to shut down my kidneys before carting me off to surgery.
The demands made on hospital staff by patients like me, with these types of infections, place a significant burden on healthcare resources and one medical publication says it accounts for 40% of total ICU expenditure.
When I showed some of those same doctors who had treated me images and descriptions of Medasorb Technologies’ (MSBT.OB) flagship Cytosorb therapeutic device, they just about all asked the same thing:
“Is this real?”
“We could really use something like this,” said others.
These days, the first-line treatment doctors rely on to try to eliminate the underlying infections with antibiotics. Indeed, I remember having six or eight different antibiotic drips going into a main line and my blood was being tested every few hours in an effort to monitor how my body was responding.
Depending on the patient’s clinical status, additional therapies are initiated, including drug therapy and supportive care, such as mechanical ventilation and kidney dialysis.
There has been considerable excitement recently amongst critical care clinicians who care for patients like me. For the first time there are trials showing positive results involving new therapeutic interventions like Medasorb’s. I spoke to Phillip Chan, MD, PhD, the CEO of Chief Executive Officer of the company. Dr. Chan is a Board-certified internal medicine physician with a strong background in clinical medicine and research, having completed his residency at Harvard Medical School at the Beth Israel Deaconess Medical Center. Dr. Chan received his MD/PhD from Yale University School of Medicine and his BS in cell and molecular biology from Cornell.
BioMedReports: Can you tell us about your company?
DR.CHAN: Sure, well Medasorb Technologies Corporation is a publically traded clinical trial stage therapeutic device company working to save lives through blood purification, that’s essentially what we do. At Medasorb we’ve developed a highly bio-compatible, porous, polymer bead purification technology that can remove things as small as drugs and toxins from blood and physiologic fluids. Right now we are currently conducting a 100 patient, randomize controlled clinical trial in Europe with our flagship product CytoSorb to treat patients with severe sepsis which is often called “overwhelming infection”.
CytoSorb is a highly efficient cytokine filter designed to treat severe sepsis by reducing potentially deadly cytokine-storm which is a well known major cause of organ failure and mortality with this disease. We’re currently driving to complete our European sepsis trial and with a hopeful positive outcome, plan to obtain C Mark approval for CytoSorb in the EU and begin commercializing it this year in fact.
We plan to take the data from this trial and present it to the FDA who has already approved an IDE application and investigational device exemption application that they approved in 2007 to run a limited sepsis study and look to them to now begin a pivotal study in the US in either late 2010 or currently 2011 to allow commercialization in the United States as well.
We recently announced preliminary positive proof of concept in humans, using Cytosorb to treat severe sepsis patients in the setting of lung injury in a 22 patient randomized control pilot study. We reported a summary of clinical data from all 13 patients that had fully monitored, completed data sets – this is 7 treated, 6 control patients – that demonstrated improvements with Cytosorb treatment in key clinical endpoints. So we think the therapy has been safe. There have been no serious device related adverse events in more than 500 human treatments, more than 150 of which have actually been in patients with sepsis.
So, the underlying technology is protected by a broad intellectual property portfolio of now 27 issued patents, with multiple applications pending that range from composition of matter to clinical application patents. A key part of our know-how is related to polymer production, which we conduct at our manufacturing facility in New Jersey under strict, well documented, reproducible processes that meet FDA clinical trial standards.
BioMedReports: You just said something interesting that I wasn’t aware of – you said that the Cytosorb technology can also clear a person from drug substances?
Dr. Chan: Our polymer platform technology is a highly porous polymer bead. We can change the size and the pore distribution of those pores to enable the removal of different things of different sizes. So the Cytosorb resin is actually specifically designed to remove a bin of substances in the specific weight range we call the cytokine ‘sweet spot’, typically 10 to 50 Kilodaltons (molecular weight) which is where most of the cytokines reside, and that’s exactly where Cytosorb targets. We have the ability to change those pores and pore size and pore distribution to be able to remove things that we want. We actually have a number of different resins that can remove different things from blood and physiologic fluids.
[For instance] imaging a sponge, the sponge looks very porous. We can make those pores very large or very small, and they trap things that are either very large or very small respectively.
BioMedReports: What is the market potential for this product. Can you tell us a little about that?
Dr. Chan: Severe sepsis is often called overwhelming infection and is one of the leading causes of death in the world. It afflicts people of all ages, particularly the very old and the very young, and it also afflicts all walks of life and all ethnicities. Unfortunately, all of us on the phone and elsewhere know someone who has developed a severe infection. It could be something as catastrophic as a ruptured appendix, or something more common as pneumonia, maybe a bad urinary tract infection or even influenza where the infection has gotten out of hand and sent that person to the intensive care unit on life support, with failing critical organs like the hearts, lungs, and kidneys. So this is severe sepsis and it afflicts more than a million people in the United States, roughly 1.5 million people in Europe, and an estimated 18 million people worldwide every single year. Despite the best medical care here in the United States, one in every three patients die of this disease, and in fact, more people die of severe sepsis in the United States than either heart attacks or strokes or any single form of cancer, so it’s a major unmet medical need.
Without better treatments for severe sepsis and its more deadly cousin septic shock, which has a mortality rate of about 50% or more, the numbers are only expected to grow with trends like an aging population and an increase in antibiotic resistant bacteria, the increased use of implantable devices like artificial hips and knees, diseases like diabetes and cancer, all put people at high risk of infection and sepsis, and all of these are driving the incidents of sepsis higher. So right now, Cygress? From Eli Lilly (NYSE: LLY) is the only product approved in the United States or Europe to treat to treat severe sepsis. It is a good drug, but it has had limited adoption by clinicians because of concerns about cost, efficacy, timing of use as well as potentially deadly side effects – well, I should say potentially ‘dangerous’ side effects. So this really leaves a wide open market for other sepsis treatments and we estimate that the total addressable market for Cytosorb in the US and the EU to be collectively about $6 to $8 billion dollars. We also believe that China and India represent extremely large follow up markets for us.
BioMedReports: You know it’s interesting, we spoke to doctors about your technology to get their feel for it and the reaction we heard most was “Wow, is this real? And if it is, we could really use something like this.” Do you get the same type of reaction out there?
Dr. Chan: We do. We talked to a number of thought leaders in this space. As clinicians should react, they were cautiously optimistic. They wanted, obviously, to see data, but they felt that this was really an approach worth pursuing and an approach that could actually really work. And so hopefully with some of the data that we’ve shown from our pilot study, we’re getting to that point.
BioMedReports:What is the potential impact that Medasorb can have in that market we just talked about?
Dr. Chan: I think that to understand how our science and technology works, it’s important to understand the path physiology of severe sepsis. Severe sepsis is really caused by two problems. One, is the infection, which can often be treated by antibiotics or other types of agents and can be addressed effectively. However, the other facet of sepsis is really the body’s immuno response to the infection. Normally the body produces things called cytokines that help stimulate and regulate the immune system, and they’re normally helpful. But in severe infection and in many people, the body’s immune system goes haywire and produces massive amounts of these cytokines to point where they’re no longer helpful but in fact, they are actually toxic to the body and can directly kill cells and damage organs leading to organ failure and in many cases, death.
So for instance, certain cytokines can cause blood vessels in the lungs to become leaky, allowing inflammatory fluid, cells and other cytokines to fill up the lungs and the person drowns in essentially his or her own fluids. Cytokine storm can also lead to hemodynamic collapse, where the heart can no longer get blood and oxygen to critical organs, leading again, to organ injury. Cytokine storm can also shut down the kidneys, which is another major risk factor for death from severe sepsis. So the role of cytokine storm in sepsis is widely accepted by clinicians and researchers, and has been very well researched, and I always point to the fact that if you do a pub-med search on cytokines and sepsis you’ll literally bring up 10,000 articles.
To drive the point home, there was a Phase I study done by another company in 2006 that was reported by the New England Journal of Medicine. What they had developed was a monoclonal antibody that was designed to stimulate the immune system to treat cancer. When they actually injected this antibody into six healthy young male volunteers, who did not have infection or cancer – they were healthy, they all developed cytokine storm and then all developed the hallmarks of severe sepsis including acute lung injury, renal failure, clotting disorders, and in fact, two of the patients, two of the volunteers who had the worse cytokine storm actually developed severe septic shock and acute respiratory distress syndrome.
This is just an example of how it is not the infection, but rather the cytokine storm that causes multi-organ failure and sepsis. The reduction of cytokine storm has been the Holy Grail for the industry for the past 2 to 3 decades, and unfortunately most of the approaches that have been tried have only been capable of removing one cytokine or one inflammatory mediator at a time. The problem is that different cytokines have overlapping functions and there’s so much redundancy in the immune response that if you remove one cytokine, even if it’s an important one, twenty others will take its place. So what is really necessary is a broad spectrum approach to try and remove cytokines across the board, and reduce them to a level where they are no longer toxic, but not reduce them so much that they can no longer help the body fight infection. And that technology has not been available until just recently, and with Cytosorb, we are one of the leaders in that field.
Cytosorb is a very effective cytokine filter that can broadly remove cytokines from blood. The treatment is very simple. You use a standard dialysis machine found in most hospitals by leading vendors like Baxter, B. Braun and others, to essentially pump blood out of the body through our cartridge. The blood goes directly through our cartridge and contacts the resin. Cytokines are absorbed and removed from blood and that purified blood is then put back into the body. We treat for 6 hours a day for 7 days each day with a new device. We have the ability to treat an entire person’s blood volume 20 to 30 times over the course of a 6 hour treatment. So the goal is really to reduce cytokine storm, prevent and limit organ damage and allow the body time to heal and recover.
We believe that our device is extremely effective at removing cytokines from blood. We know this from our invitro studies that we’ve done where we can remove 50 to 70% of certain cytokines in the first hour of treatment, and over the course of four hours actually remove 90 to 95% of certain cytokines.
In our bench top circulation system that simulates treatment. Our polymer resin is highly hemo-compatible. It meets what is called the ISO-10993 standard for 30 day medical device implantables. That includes things like bio-compatibility, hemo-compatibility, cyto-toxicity, geno-toxicity, acute sensitivity and other factors. Our device also has massive capacity unlike a standard hemo-dialyzer that has very limited capacity to bind cytokines because of very limited surface area. A single one of our cartridges has 7 football fields worth of surface area in which to bind cytokines. That is really important and a major differentiator between our technology and others based on that capacity because you need massive capacity to impact cytokine storm.
Our technology is also what we call a ‘razor blade in other people’s razor’ model, because it is compatible with standard hemo-dialysis equipment. It also contains no cells, no antibodies, nothing that can degrade over time, so it has excellent shelf life stability. We currently have 3 year shelf life stability at room temperature. It really does have a number of significant advantages over other technologies, most of which don’t work.
BioMedReports: Let’s talk about the trials in Europe. Has it been easier to accrue patients there then if you had done the trials in the US for example?
Dr. Chan: We continue to make good progress. We’re working with a stellar group of experienced and motivated investigators, many who are thought leaders in critical care in Germany. That’s very important. Germany, as you know, is the largest medical device market in the EU and the 3rd largest in the world, so it makes a great first market for us. There have been a number of issues related particularly to distance, language as well as time differences that pose a number of different challenges, but we’ve learned to adapt.
BioMedReports: Tell us about any additional goals for the company for 2010?
Dr. Chan: I think that is the major goal and that is the event that will drive the greatest shareholder value for the company, the successful completion of our trial as well as getting C mark approval. We have a number of other initiatives under way that I can’t talk about right now but we hope those will also bear fruit for the company and represent a potential upside for investors.
BioMedReports: What are the challenges you see for the company in 2010?
Dr. Chan: One of the major challenges for us is that we have a lot going on at the company with a lot of moving parts. There are a lot of things we need to accomplish this year including completing trials, strategic partnership discussions, a C Mark approval, beginning commercialization, regulatory discussions with the FDA, other things along those lines. I would say that we do have a very strong management team and we are working diligently to execute on our vision. We’re in the midst of preparing our C Mark application to try and speed approval if we complete our trial successfully.
BioMedReports: Have you discussed any strategic partnerships to go to market or to do the trials for example?
Dr. Chan: If our technology works as we hope, it really has the potential to be a blockbuster product that can impact the top and bottom lines of most potential strategic partners. We have a very active business development program under way at the company that’s been going on now for more than a year.
Cytostorb is an extensively patented product. It has a highly profitable business model. It’s in a market that has little competition and literally has a world of opportunity in front of it. We believe it’s a technology that is attractive to potential investors and hopefully with positive data from our trial we can make something happen there, but we aren’t dependent on a strategic partnership. Whether we partner with a larger company or take the product to market directly, we’re prepared to do either.