When architect and developer Harold Kent designed the Deer Park Drive office park in the early 1980s (see separate story, this page), he hoped the place would become a center for innovation. More than 30 years later, there are 52 small companies at work behind the park’s funky round windows and modernist sloped glass panels. One of them is even developing a product that the company believes has the potential to save “millions” of lives, and put a science-based twist on a prescientific idea.
There are many ways to die after a traumatic injury. But once a patient’s bones are set, his wounds closed, and his blood replenished, a huge threat still remains, and it is one that, historically, physicians have been able to do very little to stop.
Nearly half of all deaths in hospital intensive care units are blamed on organ failure, which is often the result of massive inflammation due to the way the human body responds to injuries. Once a patient is stabilized after a car accident, for example, the injury has triggered such a severe inflammatory response that several days later, the patients often develop organ failure. Deadly conditions such as sepsis, trauma, pancreatitis, lung injury, and others are all accompanied by massive inflammation.
Among the most important driving forces behind this inflammation are proteins called the cytokines. Cytokines are released by the immune system in response to infection and injury and normally mount a well-orchestrated defense of the body. But in life-threatening illnesses, the cytokines are produced at such massive levels that they no longer help the body heal. Instead, they can cause fatal inflammation and organ failure. This deadly event is called a “cytokine storm.”
Since the dawn of medicine, doctors have had an inkling of this, and have been trying to remove poisons from the bloodstream.
“The concept of removing toxic materials from the blood is not new. In fact the concept dates back to the age of Hippocrates,” says Dr. Phillip Chan, CEO of Deer Park Drive-based medical device company CytoSorbents. “They knew that ‘evil humors’ in the blood were causing disease. At that time, technology was primitive. They used bloodletting, leeches, other types of things to remove the toxic blood from patients. But these crude methods only led to worsened outcomes. Fast forward thousands of years and with the advent of dialysis, blood purification became a reality. Only recently has there been an ability to actually remove cytokines from blood, and CytoSorbents is one of the leaders in this field.”
Chan hopes his company, CytoSorbents, has finally discovered a good way to make the cytokine storm abate and has recently moved closer to the all-important tests on humans in the United States to see if the treatment can help prevent organ failure. Just announced: FDA approval of a U.S.-based human pilot study — initiated by the Air Force — using Cytosorbents technology to treat a condition that can lead to kidney failure. The study is expected to begin this year.
“Cyotkine storm has long been known as a phenomenon in critical illnesses. But physicians lack the appropriate tools to be able to control it. We have now introduced into the European market a very effective filter for controlling cytokine storm with the goal of preventing or treating organ failure in these patients,” Chan says.
Current methods of blood purification are inadequate against the cytokine storm. For example, dialysis machines work by removing blood from the body and passing it through a membrane filter before returning it to circulation. However, in the case of a cytokine storm, the membranes, which have a total surface area about the size of a kitchen table, quickly become saturated, so they can’t be used in many cases where blood toxins need to be removed. The membranes’ pore size is also too small to be effective against cytokines.
That’s where the device marketed by CytoSorbents comes in. The CytoSorb cartridge attaches to a standard dialysis machine, replacing the membrane filter. The dialysis machine removes, purifies, and recirculates blood, but where the new cartridge differs is the method of purification. The CytoSorb cartridge is filled not with membranes, but with thousands of tiny bio-compatible highly porous polymer beads, each the size of a grain of salt, that contain millions of pores and channels that trap the cytokine molecules but let blood cells go around.
Chan says these polymer beads are the heart of the CytoSorb technology. The total surface area of the beads in a Cytosorb cartridge is equivalent to that of seven football fields, allowing it to absorb many more toxic molecules than a membrane would. Over a six-hour period, a patient’s entire volume of blood goes through the machine 20 to 30 times.
The CytoSorb filter, which Chan says is the world’s first specifically approved out-of-the-body cytokine filter, is already in use in Europe, where it has passed clinical trials and has been approved for commercial use. Doctors are using the device in various European countries, mostly Germany, Austria, Switzerland, the UK, Ireland, and Turkey.
“There have already been many case reports where Cytosorb has been able to improve clinical outcomes and help patients with many different illnesses, such as sepsis, infections, burn injuries, trauma, lung injury, liver failure, cardiac surgery, and others,” Chan says.
Chan says the company has conducted clinical trials as well as clinical usage, for a total of about 1,000 human treatments. In the most recent clinical trial, the one which won the device approval for use in Europe, the Cytosorb was tested on 43 critically ill patients. Each of the 43 patients received either seven days of Cytosorb treatment plus standard-of-care treatment, or seven days of standard-of-care treatment only. Eighteen patients received CytoSorb treatment. There were 25 patients in the control group that did not get CytoSorb. The patients all had a septic shock, and all were on mechanical ventilation due to lung injury, with two-thirds of them having acute respiratory distress syndrome and another third also having kidney failure.
Normally, many patients with this combination of conditions die within days. Mortality in a population with multiple organ failure is as high as 30 to 50 percent over 28 days. Of the patients in the untreated control group with high cytokine levels — a cytokine storm — 63 percent died, whereas none of the patients who received CytoSorb treatments died.
In the same trial, a sub-group of patients older than 65, suffered a 36 percent death rate after two weeks, whereas none in the treatment group died in that time.
Although those results are promising, Chan says more work will have to be done to prove the efficacy of his device beyond all doubt of the medical community and to win FDA approval. In the world of clinical trials, 43 patients is relatively small.
“We need to do larger scale studies to prove efficacy,” Chan says.
The company’s trial with the Air Force involves a clinical trial of the filters, in which CytoSorb will be used in a randomized trial of 30 trauma patients at the Brooke Army Medical Center in San Antonio, with the goal of preventing a disease called rhabdomyolysis. The disorder is caused when crushed muscles release myoglobin proteins into the bloodstream in large concentrations. This condition can lead to kidney failure.
The technology behind the cartridges was invented by a Russian scientist. In the early 1990s, CytoSorb, then known as Advanced Renal Technologies, bought the invention and began developing it into a commercial product. Chan says he expects it to be at least four years before it can be approved for use in American hospitals. The military, however, has shown interest in it. In addition to the Air Force trial, the Defense Advanced Research Project Agency (DARPA) and the Army are both funding technology developments, for a total of about $5 million, to see if it could be effective for illnesses such as sepsis burn injury and trauma. Chan says CytoSorbents has spent about $70 million since 1997 developing the technology.
In addition to the company’s own studies, there are more than 15 investigator-initiated studies planned, some of them starting this year, and Chan says 80 opinion leaders in Europe are using CytoSorb or plan to use it in clinical trials. The company’s stock, as of this writing, was about 12 cents a share, and the company had a fully diluted capitalization of about $60 million.
Chan grew up in Rockland County, outside of New York City. His father was a pharmacologist developing cardiovascular drugs, and his mother a homemaker.
A 1992 graduate of Cornell, where he studied cell and molecular biology, Chan earned an M.D. and PhD from Yale School of Medicine and completed his internal medicine residency at Harvard’s Beth Israel Deaconess medical center and became a board-certified internal medicine doctor before going into business as a venture capitalist. He led healthcare and life science investments at the $80 million NJTC Venture Fund.
Chan joined Cytosorbents in 2009 and has been CEO and board member ever since.
CytoSorbents is not Chan’s only business venture — he also co-founded a company called Andrew Technologies that makes advanced liposuction devices. The company currently has FDA approval for a device called HydraSolve. He says his goal was always to be a clinical researcher, but that he always had a strong interest in business, too. Investing in venture capital proved to be an excellent combination of his scientific and business interests, Chan said.
The company has 21 employees between its German office and its Deer Park Drive headquarters, where they make the actual cartridges. The facility in Monmouth Junction is ISO-13485:2003 compliant.
“We look to fund our U.S. pivotal trial in the form of either direct sales of equity or through partnership with a large corporate partner,” he says.
The upcoming trial with the Air Force is described by Chan as a “major announcement” of “a significant milestone for CytoSorbents.” He notes that it is the first human CytoSorb study to begin in critically ill patients in the United States. “We are confident that CytoSorb treatment will be easy to implement, after now having safely completed more than 1,000 human treatments, mostly in Europe, including a number of treatments in trauma patients,” says Chan. “If successful, the trauma and rhabdomyolysis application could represent yet another avenue to seek CytoSorb approval in the U.S.”
One thing is for sure: Lots of eyes will be focussed on another company on Deer Park Drive.
CytoSorbents Inc. (CTSO), 7 Deer Park Drive, Suite K, Monmouth Junction 08852; 732-329-8885; fax, 732-329-8650. Phillip Chan, CEO. www.cytosorbents.com.