You’ve heard of liquid biopsy – now get ready for breath biopsy. Owlstone Medical is in the vanguard of companies developing breath tests to screen for cancer, and has just kicked off a 1,400-patient study in colorectal cancer.
Breath tests for single compounds in non-cancer indications already exist, says Owlstone’s chief executive, Billy Boyle, and these hint at the promise of breath testing. “But they can’t analyse multiple compounds at the same time, which you need to do to detect cancer,” he says. “We’re taking tentative steps, but I think we will be the first to make significant headway in the diagnostic applications which are so problematic.”
Screening for colorectal cancer is indeed problematic. The gold-standard diagnostic is colonoscopy, but this is unpleasant and compliance is low. Current screening techniques include faecal immunochemical testing (FIT) or flexible sigmoidoscopy, a less invasive but less thorough form of colonoscopy. The former has the advantage of being very cheap, but both techniques suffer from poor levels of patient compliance.
The big screen
A branded faecal test, Exact Sciences’ Cologuard, exists but is not markedly more accurate than FIT and is much more expensive. And a blood test, Epigenomics’ Epi proColon, is also available and compliance is high, but it is still more expensive than FIT (Double whammy is Exactly the wrong prescription for Cologuard, October 7, 2015).
The table below offers a summary of these methods’ pros and cons. The figures come from different studies, so are merely illustrative.
|Colorectal cancer screening techniques|
|Sigmoidoscopy||Near 100%||Near 100%||Around 70%||1,200|
|Faecal immunochemical testing||74%||95%||Around 85%||30|
|Cologuard (branded faecal test)||92%||87%||67%*||600|
|Blood test (Epi Procolon)||71%||81%||99.5%*||150|
|Breath testing||88%**||Not disclosed||Not disclosed||Not set|
|*Claimed by companies; **in early trials.|
Owlstone must negotiate this screening minefield, and will only see meaningful success if it can match FIT.
“We’re still working on the health economics,” says Mr Boyle. “Faecal-based tests cost tens of pounds – we need to be in that ballpark for it to be economic especially when considering it as an initial screen. We would need it to be competitive with other screening approaches but improve the performance.”
The test employs a technology called a field asymmetric ion mobility spectrometer (Faims), which works by detecting volatile organic compounds in a patient’s breath, Mr Boyle explains.
“You have altered metabolism in cancer, which means you have altered metabolites – the chemicals are subtly different. They enter the bloodstream, and the lungs are a really good mechanism for exchange of chemicals between blood and the airways, so with each exhalation we collect these chemicals from breath,” he says.
He adds that, like liquid biopsies, the test can allow doctors to track how a patient is responding to treatment.
Mr Boyle says the company is mostly concerned with the test’s sensitivity, particularly in detecting early-stage cancer. But payers will be looking at specificity. Colonoscopy is very accurate but also very expensive, and a screening test will only find a market if it can rule people out, cutting the number of colonoscopies performed. Owlstone has not released specificity figures but Mr Boyle said that in the current trial, called Intercept, the company would be looking for specificity of at least 80%.
A possible danger here is that the test could appeal to more patients than FIT, but with a similar rate of false positives result in many more patients being sent for unnecessary colonoscopy – payers’ worst nightmare.
Faims at last
The test is still some way from market. Intercept ought to report in late 2018, but Owlstone will need to do a subsequent study to prove its use in the screening setting before it can get CE mark. That study would be larger still – 10 times the size of Intercept, Mr Boyle says.
How will Owlstone afford such a trial? It recently closed an $11.6m funding round, taking the total it has raised to $21m, but is in fact already revenue-generating (though not yet profitable) thanks to its business selling research instruments and services. For example, it works with big pharma companies to identify likely responders to novel therapies, including for asthma drugs.
The company intends to partner for future development and commercialisation, Mr Boyle says. As well as the colorectal cancer test it is also developing a breath test for lung cancer; this is in a trial called Lucid which will enrol 3,000 patients. And it could be adapted for other cancers and indeed non-cancer indications.
“Our goal is to be the leader in this new diagnostic modality, and work with partners where it makes sense, but fundamentally grow the business ourselves,” Mr Boyle says. The company appears well placed to make a success of breath biopsy if any group can. But the challenge of producing a colorectal cancer breath test as cheap and accurate as FIT should not be underestimated.