Chris Anderson

Pressure on clinicians to more accurately diagnose and prescribe expensive new drugs is rapidly advancing Dx development.

In oncology, more precise treatments for many different forms of cancer are in the offing, a prospect that makes oncologists the envy of other healthcare professionals. Already, cancer companion diagnostics can show doctors the specific drug that will be most effective in treating a particular subtype of cancer. Unfortunately, such specificity does not yet exist for diagnosing autoimmune diseases such as lupus, Sjogren’s disease, and rheumatoid arthritis.

More definitive diagnostics are needed for autoimmune diseases. Technologies capable of predicting drug responses would be especially welcome. But there are many development challenges: autoimmune symptoms are similar to symptoms of many other diseases; the disease pathways for many autoimmune disorders aren’t clear; and autoimmune diseases are systemic—unlike solid tumor cancers, which start as highly localized disease.

“[Autoimmune disease] is a different [problem]. In the case of cancer, we have developed a model where [an identifiable] pathway has gone awry, and because the pathway has gone awry we can go after the pathway,” says Steven Binder, Senior Director, Technology Development Clinical Diagnostics Group, Bio-Rad Laboratories. “In the case of autoimmune diseases, we don’t always know the pathways, and the ones we are really concerned about are systemic. The pathway is screwed up all over your body.”

But despite the challenges to developing more targeted diagnostics for auto-immune diseases, Frost and Sullivan projects that the worldwide market for autoimmune diagnostics will grow to more than $1 billion worldwide by 2018, up from about $712 million in 2012. Much of this growth, which is expected to be driven by new and potentially expensive drugs targeting autoimmune disorders, will pressure clinicians to more accurately diagnose and prescribe therapeutics that have the best chance of providing effective treatment.

Forging More Objective Test Methods

Much of the activity in creating new autoimmune disease therapies is focused on rheumatoid arthritis (RA). Diagnostic companies are working to create new tests that can detect the disease earlier and also provide risk assessment profiles of patients that are more or less likely to suffer permanent physical damage as a result of the disease.

One diagnostic that measures RA disease activity is Vectra DA from Crescendo Bioscience. Vectra DA consolidates multiple biomarker results into a single score, a number between 1 and 100 that classifies RA disease activity as low, moderate, or high. The Vectra DA score also correlates with the risk of permanent joint damage.

According to Eric Sasso, vice president of medical affairs with South San Francisco-based Crescendo, the test can help doctors treating patients with RA determine if their current treatment regimen is helping to reduce disease activity and thus future joint damage. Using this information, doctors can choose to either stay with the current treatment program or switch to other drugs in an attempt to find a more effective treatment for a particular patient.

Sasso suggests that the test’s ability to detect future risk of joint damage may lead Crescendo to other insights about RA and how to better detect it, or detect it earlier. “Knowing that the test is closely associated with the risk for future joint damage provides additional evidence that the test is measuring processes that are intimately involved with the pathological processes of rheumatoid arthritis,” he notes.

Another company targeting the RA diagnostic market is Dortmund, Germany-based Protagen Diagnostics, which uses its multiplexed biomarker identification SeroTag to detect and validate autoantibodies implicated in a range of autoimmune diseases. The goal at Protagen is to use these autoantibody markers to develop companion diagnostics for RA and to be able to subgroup RA patients, much as cancer companion diagnostics identify subtypes of cancer.

“[The immunology diagnostic process, like] the oncology diagnostic process, [can take advantage of ] companion diagnostic tools … to identify a specific subgroup of patients. [A] specific genetic mutation or, in the case of autoimmune disease, a specific autoimmune marker [may define] a subgroup,” explains Georg Lautscham, Protagen’s Chief Business Officer.

Unlike companion diagnostics in cancer, though, currently available diagnostics for RA drugs do not give black-and-white answers. Straightforward binaries are not typical of autoimmune disease companion diagnostics.

Aiding Drug Development

While current autoimmune diagnostics may not rise to the level of a true companion diagnostic, they are nonetheless sought out by pharma companies looking to measure drug candidates’ efficacy. Also, drug companies are seeking to target slices of the population of patients suffering from an autoimmune disorder as opposed to the entire population of people with the disease.

“Eli Lilly had a Phase III failure [of a] systemic lupus erythematosus (SLE) [drug]. [The company was] developing for the full patient spectrum, and [the] compound came just short of being able to reach that preliminary endpoint,” Lautscham says. Such a failure, in the context of increasingly stringent regulatory demands (drug approvals appear to be contingent on higher response rates in Phase III trials), pharma may not be looking to develop drugs that address the full market.

“So, based on these failures and based on regulatory demand, more and more companies will [follow] the … route [established in] oncology,” Lautsham concludes. “They will develop companion diagnostics for their compounds to enable the development of more targeted therapeutics that have a greater likelihood of yielding a positive clinical outcome.”

Sasso sees the same potential for the diagnostics being developed at Crescendo. “The main hope is to be able to predict with greater certainty the likelihood of response [and perhaps even] influence decision making, but we are not on the verge of having any kind of binary statement around whether any drug should or should not be used for RA,” he admits.

If breakthrough diagnostics for RA could be developed, doctors could move beyond disease activity scores compiled on the basis of patients’ subjective pain assessments. (The DAS28 score, for example, is a 28-joint assessment.) Instead, doctors could rely on objective biomarker-based approaches that have been validated for the prediction of responses.

Using predictive RA diagnostics “is a major shift in the management of patient care,” Sasso asserts. “It is a shift toward greater inclusion of objective measures to assess disease activity, both to better understand the disease itself and to objectively predict the risk of radiographic progression while optimizing [patient] care [and personalizing] treatment decisions.”

Chris Anderson is the former Chief Editor of Drug Discovery News, which he helped launch in 2005. ([email protected])

This article appears in the December 10 issue of Clinical OMICs. For more content like this and details on how to get a free subscription to this digital publication, go to

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