How long has it been known that measuring certain parameters in a patient's breath may be useful from a diagnostics perspective?
It was back in the 1960s that scientists first started to understand that breath could be used to find out different things about diseases and other factors.
I’m sure you’re familiar with alcohol breath testing, which was patented back in the ‘50s and has been used since the ‘60s.
Back in the ‘70s, some research by Linus Pauling showed that certain parameters in the breath could be used to diagnose different diseases. However, the test that is performed today (using the carbon 12: carbon 13 ratio) only really started to be used in the mid-to-late ‘90s and only became more prevalent in about the mid-2000s.
Today, the test is used to analyze the level of CO2 in a patient’s breath. We look at two different isotopes, carbon 12 and carbon 13.
Why is the detection of H. pylori bacteria particularly important?
H. Pylori was actually discovered back in 1982, but the link was only made between H. Pylori and ulcers many years later by two Australians. They were awarded the Nobel Prize for their finding in 2005.
It’s important to detect H. Pylori because it can be fatal. In a small but still significant proportion of people, infection with H.pylori leads to gastric cancer.
Some patients are unaffected by H. Pylori, but others will develop ulcers that can bleed and obviously cause other damage and in the worst case, cancer.
In fact, the World Health Organization (WHO) considers H. Pylori a carcinogen. They’ve identified it as a huge problem, especially in third world or less developed countries.
Please can you outline Exalenz Bioscience’s BreathID test?
When we designed the test, we wanted to make it as simple as possible so that it could be carried out in a physician’s office, as well as in a laboratory.
With this test, a patient can visit their doctor, who places two plastic cannula in their nose (similar to when patients are given oxygen) and then they just breathe normally for about a minute. They then drink a substrate that contains urea tagged with carbon-13.
It’s a only a small drink, of about 4 or 5 ounces, and when they have drunk it, the urea interacts with any H. Pylori bacteria present in the stomach.
This interaction sets C-13 free, which is then absorbed into the bloodstream and subsequently exhaled in the CO2.
Everybody has some C-13 in their CO2, but the device immediately flags up an increase in C-13 because the usual ratio between C12, the most common carbon isotope, and C13 is the same in everybody.There is a cut-off value programmed into the Breath ID device and if the patient’s measured value is higher than the cut-off, they are positive for H. pylori.
If a person has H. Pylori, the device will show a very high level of C-13 after they drink this substrate. The whole process is painless, non-invasive and can be performed in a doctor’s office in around 10 to 15 minutes.
Immediately after the test, the doctor will know if a person has H. pylori, in which case they can prescribe antibiotics and initiate treatment right away.
The course of antibiotics lasts for about 2 to 3 weeks, after which the patient can return for a follow-up test to make sure the infection been eradicated.
If the H.pylori is still present, another course of antibiotics can be prescribed. It’s therefore a very simple, user friendly test that any operator can perform after receiving minimal training.
It was recently announced that Exalenz Bioscience would be starting a study examining the potential of BreathID in the diagnosis of Clinically Significant Portal Hypertension (CSPH). Please can you give a brief overview of this study?
This is a very exciting opportunity not only just for us but for clinicians all over the world. In the United States, millions of patients have cirrhosis and, as time goes on, they can develop a condition referred to as clinically significant portal hypertension (CSPH).
Currently, the only way to detect CSPH is by using a very invasive procedure to measure the hepatic venous pressure gradient (HVPG). This involves passing a catheter through the patient’s jugular vein and then introducing some radioactive material, which is then scanned.
This is a very invasive, difficult, and potentially dangerous procedure to perform, but it’s the only way to diagnose CSPH. However, our preliminary studies have shown that our test for liver function correlates very well with CSPH.
For quite some time, we’ve been trying to agree a protocol with FDA to use our breath test on hundreds of patients prior to their HVPG procedure, to see if the test could be used to diagnose CSPH.
The clinical trial will involve two phases. During the first phase, we’re going to collect data on 200 patients across five clinical sites: four in Europe and one in the United States.
We will use the data to develop an algorithm that will hopefully correlate HVPG to our breath test, which will take about 12 months. We started just this month so the first phase of the trial should be complete about a year from now.
We will then need to validate the algorithm in the second phase, which will involve a larger population of around 300 to 400 patients across five to seven sites. If we’re successful, we’ll submit our findings to the FDA to get the test approved for diagnosing CSPH.
If it is approved, patients could use our breath test instead of undergoing the laborious and risky procedure that is currently used to diagnose HVPG.
When do you expect this study to be complete and what will be the next steps following on from this?
The first phase will be completed in about 12 months and the second phase will take another 12 to 14 months, which brings us to 2017.
We would expect to submit to the FDA around that time and hopefully get the test on the market by the second half of 2017.
What impact do you think a breath-based test for CSPH would have?
We think it would have a very big impact because physicians would prefer this less dangerous, less invasive procedure for gathering information and managing patients with cirrhosis.
The test would be particularly useful in cases of CSPH, because the test would help indicate whether treatment is needed to control the portal hypertension, whereas without the test, a doctor may not have enough information to change treatment of the patient.
Are you planning to launch similar studies for additional liver indications?
Yes, we have two or three other indications that we are planning studies for. The first one is a very serious condition called nonalcoholic steatohepatitis (NASH). The difficulty right now is determining who has NASH and differentiating it from another condition called nonalcoholic fatty liver disease (NAFLD).
In the US, about 30 to 35 million people have NAFLD, but of those, a smaller percentage have NASH.
Currently, the only way to diagnose NASH is through a biopsy. Again, this test is very invasive and associated with its own set of risks, but also you can’t biopsy 30 million people… that just doesn’t make sense.
We’ve developed a non-invasive breath test to diagnose NASH and we will be starting a study early next year that will follow a format similar to the CSPH study.
First, we’re going to develop an algorithm using data collected on a couple of hundred patients and then we will use that algorithm to validate the test.
We are also going to work with some pharmaceutical companies that are developing therapies for NASH, to help validate the test.
Some of the drug companies are also starting trials, around the middle of next year, so those will probably all come together in 2017 as well.
The NASH study is a little bit behind the CSPH study, so we’re probably talking about the year 2018 for approval there, although it may be adopted earlier for use as a secondary endpoint in these pharmaceutical clinical trials.
There are also couple of other indications I have not discussed yet. We have a test for hepatocellular carcinoma, which is liver cancer. Prevalence of this condition is high in China, so we are planning to start a trial in China next year for the liver cancer test.
Finally, we’re going to be working alongside the Acute Liver Failure Study Group in the U.S next year to look at using the test to help patients with acute liver failure. These are very sick patients who are waiting for transplants.
What are Exalenz Bioscience’s plans for the future?
Our plan is to become the diagnostic provider for gastrointestinal indications and liver indications. There are several disease states where a non-invasive and easy-to-use diagnostic test is needed. Our plans are to become the leading company in that field and to continue to grow.
We have just attended the annual meeting of the AASLD, that’s the American Association for the Study of Liver Disease.
We talked with many opinion leaders and pharmaceutical companies and I can tell you that the demand for a non-invasive breath test for liver function is huge. Everybody is really anxious for us to complete the study and get the product on the market, so there is a lot of excitement surrounding this.
Where can readers find more information?
http://www.exalenz.com/
About Larry Cohen
Mr. Cohen has been an executive in the In Vitro Diagnostic industry for more than 35 years. Previously, he was CEO of SenGenix, Inc., a start-up company utilizing protein engineering technologies developed at Duke Medical Center to develop point-of-care diagnostic products. Prior to that he was President of International Technidyne(ITC), a subsidiary of Thoratec Corporation for 10 years until the company was sold to Warburg Pincus in 2010.
Prior to ITC, he was CEO of HemoSense, a start-up that focused on anti-coagulation monitoring for the professional and home testing markets. He has also held the positions of Worldwide Group VP, VP International and VP Marketing and Sales at Ortho Clinical Diagnostics, a Johnson and Johnson Company where he worked for 9 years. Prior to Ortho Clinical Diagnostics, he held leadership and senior management positions at Instrumentation Laboratory, Fisher Group, and Beckman Instruments.
He has also been President of the Biomedical Marketing Association, VP of the Raritan Valley American Red Cross and a past Board Member of Overlook Management Corp. of Overlook hospital, Summit, NJ. Mr. Cohen earned a B.S. degree with a major in chemistry from College of Emporia.
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