Sepsis is the leading cause of death worldwide according to the World Health Organization, killing 11 million people each year, many of them children, and disabling many more. But while speedy diagnosis and treatment is crucial in combating sepsis, the medical profession has no reliable and speedy test for the condition.
That is about to change, courtesy of a San Francisco-based medtech start-up. Founded in 2013, Cytovale is now in the final stages of clinical trials of a new test for sepsis that generates results in less than 10 minutes.
“My dad was a critical care physician and my wife is an anesthetist, so I’ve grown up around medicine that impacts people’s lives at their most vulnerable moments,” says Ajay Shah, one of three co-founders of Cytovale and the company’s CEO. “Right from the start, we recognised the huge need to improve early detection of sepsis.”
The problem that hospitals face the world over is that while large numbers of patients present with symptoms that could indicate sepsis, most of them don’t have the condition. Moreover, diagnosing and then treating sepsis is currently a resource-intensive process; it is not a care path to be embarked on routinely, particularly given concern about overuse of antibiotics.
Equally, however, the failure to diagnose and combat sepsis is potentially disastrous – delays in treatment can lead to all sorts of catastrophic health outcomes, including damage to the heart, lungs and other organ systems, amputations, and death. The latest research suggests the risk of death from sepsis increases by as much as 8% each hour that the condition goes untreated; indeed, 80% of sepsis deaths could be prevented with rapid diagnosis and treatment.
Against this backdrop, early detection of sepsis represents a priceless tool for healthcare professions. “We want this to be an absolutely routine test,” says Shah. “It is something that the triage nurse could administer as patients enter the emergency department.”
Cytovale’s “IntelliSep” test is based on technology developed by Shah, his co-founders Henry Tse and Dino Di Carlo, who have worked together since a stint at UCLA, and a team that has grown from four to around 50 members of staff over the past eight years. The test requires a blood sample from the patient which is then processed in a benchtop instrument designed by the company to sit in hospitals’ clinical laboratories. The machine studies the mechanical properties of the patient’s white blood cells, which differ for sepsis patients compared to those who don’t have the condition.
The results are available in less than 10 minutes, with the machine dividing patients into three groups according to their probability of having sepsis. Low-risk patients get a green rating, medium-risk patients are graded yellow, and the highest-risk cases are red. The results give emergency department doctors an immediate opportunity to decide how to proceed with treatment.
“Something like 20% of people walking into an emergency room have symptoms that might indicate sepsis, whether that’s a high temperature or an elevated heartbeat, say, but most of them will not have the condition,” Shah explains. “Doctors are looking at those vital signs upfront to make a clinical judgement, but there is a great deal more clinical work to do to make a diagnosis, and that takes time and precious hospital resources.” In many cases, those resources turn out to have been deployed unnecessarily, with sepsis ruled out; much worse, in other cases, there isn’t enough time to wait for a positive result.
Given the prevalence of sepsis, its devastating impact and the current lack of simple diagnostics, Cytovale’s technology has the potential to be transformational. But Shah and his colleagues have refused to rush to market. “We’ve been evolving this technology and its applications since 2013, and the product has undergone a series of clinical trials,” he says. “Now we are ready to make our results submission to the FDA [the Food and Drugs Administration responsible for giving regulatory approval to new drugs and tests in the US].”
That could see Cytovale launching IntelliSep commercially in the first half of 2022, with Shah just beginning to think about pricing. “We are very aware of the cost constraints on hospitals and we see IntelliSep offering value of many orders of magnitude greater than its cost,” he says. “This is all about ensuring the right patients get the right treatment at the right time.” Apart from the very obvious positives of better outcomes for patients who do have sepsis, hospitals will enjoy benefits such as reduced spending on patients who don’t have the condition, and more rapid throughput of patients presenting at the emergency department.
The scale of the commercial opportunity for Cytovale is certainly not lost on Shah. Indeed, the company has attracted a string of investors, raising more than $50m of financing. “It’s very exciting to see Cytovale’s technology progressing to the point where it can make a meaningful impact on patient care, possibly saving thousands of lives,” says Professor Michael Atar, one of Cytovale’s first advisors and lead investor. “Ever since I first heard about Professor DiCarlo’s lab at UCLA, I knew I had to get involved. His medical engineering lab contained the kernel of what has become Cytovale, and I’ve long believed their approach could provide fundamental biological insights. This collaboration will be transformative in Silicon Valley, and I’m thrilled that we’re poised to make a huge impact on healthcare outcomes, in sepsis and beyond.”
In addition, investment has has come from venture capital backers including Breakout Ventures, Blackhorn Ventures, Dolby Family Ventures and Western Technology Investment, but also from grants and contracts from the National Science Foundation, the National Institutes of Health and the US Health & Human Services Department.
The bigger picture, however, is all about saving lives. “It has been incredibly humbling and rewarding to advance the technology,” Shah says. “Something that started out as idea from two research scientists [Shah credits his co-founders Tse and Di Carlo] has evolved into something that is poised to help tens of millions of people.”