Biomarker bonanza: New molecular markers fuel diagnostic development

Until recently in vitro diagnostics, which are tests that use fluid or tissue samples, were regarded as not very glamorous or profitable compared to their well-heeled cousins:  imaging-based diagnostics, medical devices and therapeutics.  But times are changing, and while they may never command the eye-popping $250,000 price tag that some newer drugs do, for example, there are still many experts who think there could be a Cinderella story for certain types of in vitro diagnostics.

The combination of new types of tests and a greater emphasis on cost-effectiveness in healthcare delivery, could spur growth in this arena.

"IVD’s only represent 2% of healthcare costs right now, but they influence approximately 70% of healthcare decisions," says Harry Glorikian, author of Commercializing Novel IVDs.  Glorikian and others see big potential for IVDs to be better used to reduce healthcare costs, which are widely viewed as unsustainable.

In Vitro tests are run on blood, urine, tissue (including tumors), and cerebral spinal fluid. They are typically analyzed in hospital or commercial labs that process many samples per day. The world market for such diagnostics totaled more than $53 billion in 2013 and is expected to reach more than $80 billion worldwide by 2022, according to Allied Market Research.

Many of these tests are very old and relatively inexpensive. They are used for things such as evaluating the immune system, testing for infectious diseases and measuring blood coagulation. There is also a robust market for self-testing among diabetics. Roche Diagnostics, Siemens Healthcare and Abbott Laboratories are the dominant companies in the diagnostic field now, garnering almost 30% of the total market between them.

But there is a new kid on the block. The field of molecular blood- and tissue-based tests is exploding, mostly in cancer treatment but also, little by little, in other areas including cardiovascular disease and neurological disorders.

Biomarkers are essentially molecules found in blood, urine, tissue (including tumors) or cerebral spinal fluid. Until the genomic revolution, about 20 years ago, few of these markers reflected genetics. They were biochemical markers that signaled the presence of some type of viral or bacterial infection, or signals of high risk of such conditions as heart disease or diabetes.

But since the human genome was sequenced there has been tremendous progress in the area of genetic markers, also known as variants.These include simple misspellings in the DNA that lead to big changes, or extra copies or deletions of genetic message.  Studying these genetic mutations has been challenging for a long time. It cost about $2.7 billion to sequence the first human genome, which was actually a compilation of multiple genomes, but gave us a picture of a typical human DNA sequence. Since then, however, technology has rapidly advanced. "DNA sequencing has changed the entire landscape of cancer diagnostics," said Anthony John Iafrate, Medical Director of Massachusetts General Hospital (MGH)’s Center for Integrated Diagnostics.

This genomic revolution is critical, since such markers can not only detect full-blown disease, but also identify patients at high risk of either developing a disease and/or passing it on to their children.

New technologies have also made it possible to identify and test for an increasingly wider range of these genetic variations. "Next generation sequencing [NGS] has driven down the cost per human genome dramatically and led to clinical use of whole genome sequencing," explains Glorikian. "We are getting much more complex information from these tests, and that means interpretation is often as important as the quality and accuracy of the test."

That’s led to a whole new industry sector.  N-of-One, for example, is a company that partners with hospital systems, cancer centers and commercial labs to provide interpretation services for oncology testing. Using the latest available scientific evidence, N-of-One helps point doctors to the best treatments for their patients, including clinical trials. Their analysis includes looking at genetic variations and more traditional tests, such as immunohistochemistry (IHC).  "We’ve done the interpretation on scores of patient cases characterizing tens of thousands of variants across hundreds of genes," explains Jennifer Carter, president and CMO of N-of-One. 

Many such variants have already been identified as "drivers" of tumor growth. The key questions now: how many more such tumor-driving engines are out there? How do they interact? Can some of them interfere or enhance the actions of others and thus the response to therapy? N-of-One and a handful of other companies are trying to help answer these questions.

But what does the future hold?

"Naturally, regulatory developments are always going to have a big impact on the IVD industry, so we need to watch those closely," says Glorikian. "But we are also anticipating some new developments, such as FDA ‘approved’ or ‘certified’ databases that could be used to support the approval of tests."  That would be a radical change from the status quo.

Iafrate points to several areas of intense unmet need, including early disease detection, follow up for patients who have been treated for cancer and better understanding of who will develop resistance to particular drugs and why.  He points out that, for solid tumors, tools allowing a shift from tissue samples to blood tests is a big area of interest.  "In the last five to ten years, the technology has emerged that should allow us to test blood when we used to need a tissue sample," he said.  The big challenge here is that there is such a small amount of tumor DNA in the bloodstream, it’s a big "signal to noise" issue.

Carter says that on the clinical side, the future lies in part, in finding biomarkers and developing tests that will help guide combination therapies. It is becoming clearer that it may be possible to treat cancer as a chronic disease, but to do that will likely require complex combination therapy protocols, possibly including surgery, radiation, chemotherapy, targeted therapies and immunotherapies. 

One of the key industry goals right now is to find biomarkers to guide treatment with immunotherapies (e.g. PD1 and PDL1 inhibitors) – a relatively new class of cancer drugs that have provided never-before-seen results, but only in a small percent of patients so far.

Glorikian also advises companies to put greater emphasis on interoperability and transparency.  "To achieve truly cost-effective outcomes in a value-based care system, hospitals will have to share data [interoperability] and make that data available to others [transparency] as well," he says. "That is the direction we need to go."

Filed Under: Clinical Trials