News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Clinical Laboratories May Need to Expand Test Portfolios with Companion and Complementary Diagnostic Assays as More Test-Dependent Drug Therapies Enter Market

However, the distinction between how the two different types of diagnostic tests are intended to be used still confuses many physicians and healthcare professionals

Companion diagnostics are well-known to medical laboratorians. However, the new-breed of complementary diagnostics might not be as familiar. As the pharmaceutical pipeline increasingly becomes filled with test-dependent new drug therapies, medical laboratories and anatomic pathology groups may need to sharpen their understanding of companion and complementary diagnostics to broaden their laboratory test portfolios and keep pace with the growing demand for these new diagnostics.

Companion Diagnostics

Currently in the US, 30 companion diagnostic assays have been approved governing the use of 19 therapeutic drugs, according to a recent NCBI table published in Clinical and Translational Science.

The FDA defines a companion diagnostic as a “medical device, often an in vitro device, which provides information that is essential for the safe and effective use of a corresponding drug or biological product. The test helps a healthcare professional determine whether a particular therapeutic product’s benefits to patients will outweigh any potential serious side effects or risks.”

Because a companion diagnostic device is “essential for the safe and effective use” of the drug to which it has been assigned, it is identified on the drug’s product label.

The anti-HER2 drug Herceptin, for example, is a commonly prescribed breast-cancer therapy drug that in its various forms comes with one of 11 companion diagnostic devices. As a requirement of Herceptin’s Food and Drug Administration (FDA) approval, the agency requires pathologists to use a companion diagnostic test to confirm a patient’s over expression of HER2 (human epidermal growth factor receptor2) protein before prescribing Herceptin. The other HER2-directed therapies have their own assigned companion diagnostic.

Complementary Diagnostics Is a Growing Opportunity for Clinical Labs

Now, nearly two decades after companion diagnostics first made headlines, pathologists are encountering a new concept—complementary diagnostics. Unlike companion diagnostics, complementary diagnostics aid the therapeutic decision process, but are not required when prescribing the corresponding drug.

In an interview with Dark Daily, Debra Harrsch, President and Chief Executive Officer of Philadelphia-based Brandwidth Solutions, noted that the addition of complementary diagnostics adds a layer of complexity to the diagnostics landscape for pathologists and other healthcare professionals.

“The diagnostics landscape is not only expanding in size and scope, it is also becoming increasingly complex as growth in biomarker– and genomic-based test strategies fuels progress in personalized medicine,” she stated.

Peggy Robinson (left), US Vice President of ANGLE plc, and, Debra Harrsch (right), President and CEO of Brandwidth Solutions in Philadelphia, spoke with Dark Daily on the differences and values of companion versus complementary diagnostics. “The role that companion diagnostics can have in driving personalized medicine is already leaving its mark with drugs such as Herceptin. The impact of complementary diagnostics and how the two types of tests come to share the stage awaits to be seen,” they noted. (Photo copyright: Dark Daily.)

Peggy Robinson, US Vice President of ANGLE plc, a global liquid biopsy diagnostic company, explained that the lack of a regulatory link to a specific testing technology is the critical distinction between a complementary and a companion diagnostic.

“A companion diagnostic is one of the gateways for you to receive a drug,” Robinson stated in the Dark Daily interview. “A complementary diagnostic can aid your physician in helping to determine what level of therapy would be appropriate for you, but it is not required.”

Pairing Clinical Laboratory Tests with Complementary Diagnostics

In 2015, Dako’s PD-L1 IHC 28-8 pharmDX immunohistochemistry test, which determines PD-L1 protein in non-squamous non-small cell lung cancer, became the first FDA-approved complementary diagnostic, when it was paired with the drug Opdivo (Nivolumab).

At that time, Christopher Fikry, MD, then Vice President, Oncology, of Quest Diagnostics (NYSE:DGX), praised the FDA’s introduction of the first complementary diagnostic. He noted in a statement that it would “give physicians greater understanding of treatment expectations with Opdivo and helpful information to communicate to patients.”

Clinical Laboratories Can Add Value to Their Patients’ Healthcare

The challenge for clinical laboratories and pathology groups will be keeping pace with a rapidly expanding catalog of available diagnostic tests. While the number of drugs (two) with FDA-approved complementary diagnostic tests remains small, Peter Keeling, CEO of Diaceutics, a global advisory group for the laboratory, diagnostic, and pharmaceutical industries, predicts that number will be rising.

In a 2016 webinar on companion versus complementary diagnostics, Keeling pointed out that 50% to 90% of products in development through 2020 at the top 10 pharmaceutical companies are test dependent. This highlights the importance of targeted therapies designed to advance the goals of personalized medicine.

Clinical Labs Can Build Out Test Menus with Complementary Diagnostics

“Laboratorians need to understand what type of technologies they are using to employ these diagnostics,” Robinson told Dark Daily. “As laboratory managers build out their test portfolios, they should be looking at the technology and asking, ‘Can I integrate that into my laboratory?’ so that when a new test comes out, they can offer it.”

Meanwhile, healthcare professionals have more work to do to understand the differences between companion versus complementary test labeling. In his webinar, Kelly noted that in a poll of 30 Opdivo/Keytruda prescribers, Diaceutics found:

  • 40% of prescribers surveyed did not understand the differences between the PD-L1 test labels for Keytruda (Pembrolizumab), which requires a companion diagnostic, and Opdivo, which has an associated complementary diagnostic;
  • 60% were unclear about the role of complementary testing; and
  • 50% said their therapy decisions would be impacted if a laboratory used for PD-L1 testing offered only one test.

Harrsch told Dark Daily that “time will tell” whether complementary diagnostics can match the impact of companion diagnostics in improving healthcare outcomes.

Future of Complementary Diagnostics Still Uncertain

“The role companion diagnostics can have in driving personalized medicine is already leaving its mark with drugs such as Herceptin,” she said. “The impact of complementary diagnostics, and how the two types of tests come to share the stage, awaits to be seen.”

As the market for companion and complementary diagnostics expands beyond targeted therapies for oncology, clinical laboratories and pathology groups can position themselves to “add value” to their patients’ journey through the entire healthcare continuum. Robinson believes one key for pathologists going forward will be maintaining a “close working relationship” with client physicians in order to plan for future test offerings.

—Andrea Downing Peck

 

Related Information: 

Companion and Complementary Diagnostics: Clinical and Regulatory Perspectives

Current Status of Companion and Complementary Diagnostics: Considerations for Development and Launch

Distinguishing Between Companion and Complementary Diagnostic Tests

Quest Diagnostics Introduces Dako’s PD-L1 Complementary Diagnostic Test to Support Bristol Myers Squibb’s OPDIVO Anti-PD-1 Therapy for Non-Squamous No-Small Cell Lung Cancer

Companion Versus Complementary Diagnostics

PD-L1 IHC 28-8 pharmDX-P150025

Pathologists Will Benefit from Cancer Research to Describe 50 Tumor Types

Goal is to map genetic, transcriptomic, and epigenomic changes in various cancer types

Surgical pathologists are likely to gain great benefit from a worldwide research collaboration that has $500 million in funding, and whose participants plan to identify and publish data about the genetic complexities involved in at least 50 different types of tumors. It is a research project that will directly contribute to the development of new and more precise clinical laboratory tests.

This research is being conducted by geneticists from around the globe. They are collaborating to describe the genomic, the transcriptomic, and the epigenomic changes in 50 tumor types. Expectations are that this research will produce an unprecedented leap in knowledge and launch a new age in cancer research.

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“Poorly-Developed” Clinical Pathology Laboratory Tests Subject of New York Times Story

Times reporter looks at issues affecting accuracy of different breast cancer tests


Pathologists should consider a recent story about breast cancer testing in the New York Times to be a warning flag, similar to the warning flags that the Coast Guard flies along the coast to warn of an approaching hurricane. The subject of the story was “unclear tests” used to identify whether a breast cancer patient is a candidate for certain therapeutic drugs.

The New York Times story was in response to the public release of new guidelines for processing specimens used in estrogen receptor and progesterone receptor (ER/PR) testing for breast cancer. The guidelines were announced by the College of American Pathologists and American Society of Clinical Oncology (ASCO) on April 19, 2010. One goal of the new guidelines is to improve “the accuracy of immunohistochemistry (IHC) testing for the expression status of estrogen (ER) and progesterone receptors (PgR) in breast cancer” as performed by the hundreds of anatomic pathology laboratories in the United States which perform ER and PR testing.

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Roche Pays $46.8 Billion for Genentech—Now Sole Owner of Herceptin!

When Roche Holding AG (RO) of Basel, Switzerland, announced last month that it had an agreement to buy Genentech Inc. (DNA) of South San Francisco, California, it was big news. Roche had pursued the innovative drug maker since July with the primary goal of gaining access to the drugs in Genentech’s pipeline.

On March 11, Roche got the support of Genentech’s board to pay $95 per share to buy the 44% of the company it doesn’t already own. One intriguing reason why Genentech was so attractive to Roche is that the California company has a line of products and biomarkers that fit almost seamlessly with what Roche already offers, including Herceptin, HER2/neu assays, and biomarkers useful for both companies.

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Pathology and Radiology Must Prepare for Personalized Medicine

If there is one healthcare trend that will be truly disruptive to pathologists, it is personalized medicine. The concept behind personalized medicine is simple: understand the genetic and metabolic differences unique to the individual patient. Then use this knowledge to tailor a custom program of therapy, including prescription drugs, that offers the maximum potential for success while minimizing possible side affects.

Personalized medicine is closely linked to the emerging field of companion diagnostics. In combination, these two new ideas have the potential to revolutionize how laboratory testing services are used in developed healthcare systems. For one thing, clinical laboratories and anatomic pathology groups-traditionally the “go to” source for information to drive diagnostic, prognostic, and therapeutic decisions-will have serious competitors in the world of personalized medicine and companion diagnostics.

One keen observer of the personalized medicine trend is Bruce Friedman, M.D., Professor Emeritus of Pathology at the University of Michigan Medical Center in Ann Arbor, Michigan. In his popular LabSoft news blog, he defined companion diagnostics in this manner:

Briefly stated, [companion diagnostics] is a strategy pursued by some IVD companies, Roche Diagnostics in particular, whereby the company develops a gatekeeper biomarker assay. This is a lab test that serves to qualify a patient for treatment with a particular drug. The most common example of such a test is the HER-2/neu assay that is required prior to treatment with Herceptin.

Friedman, like your Dark Daily editor, recognizes that advances in genetic science and molecular technologies are making it possible for other medical specialties to crowd into the diagnostic field. He believes that the current, commonly-used definition of companion diagnostics-as primarily measurement by use of serum biomarkers-is outdated. He thinks the definition should be widened, writing in his blog that: “I personally have begun to routinely assume that diagnostics, unless otherwise qualified, should be more broadly defined to include both the analysis of serum and tissue biomarkers as well as medical imaging procedures. I have posted a number of notes about molecular imaging, which is defined in the following way in the Wikipedia:

[Molecular imaging] differs from traditional imaging in that probes known as biomarkers are used to help image various targets or pathways, particularly. Biomarkers interact chemically with their surroundings and in turn alter the image according to the molecular changes occurring within the area of interest. This is markedly different from previous methods of imaging which primarily imaged differences in qualities such as densities or water content.”

Friedman continues, saying: “I think that we now need to broaden our definition of companion diagnostics to include both the measurement of serum/tissue biomarkers as well as medical imaging and particularly molecular imaging. Such an approach also echoes my belief, expressed in a number of previous notes, that pathology, lab medicine, and radiology are becoming much more closely aligned and should now merge into a new discipline of diagnostic medicine. This broader definition for companion diagnostics also suggests that Roche, GE, and Siemens are embarking on very similar strategy in the pursuit of personalized medicine.”

All pathologists and radiologists should track this trend, which is poised to disrupt long-standing practices in their respective medical specialties. Friedman will speak on this topic at the upcoming Molecular Summit on the Integration of In Vivo and In Vitro Diagnostics in Philadelphia on February 10-11, 2009. Location is the Sheraton Society Hill Hotel in Philadelphia, Pennsylvania. Joining Friedman is a faculty of 27 other leading national and international experts in molecular imaging, molecular diagnostics, and healthcare informatics.

Speakers from such organizations as Massachusetts General Hospital, Stanford University Medical Center, MD Anderson Medical Center, UCLA Medical Center, Siemens, and the Institute for Systems Biology will provide the latest innovations in the integration of in vivo and in vitro diagnostics. Last year’s Molecular Summit attracted 225 attendees, along with editors and reporters from 15 healthcare publications. This upcoming Molecular Summit has compelling case studies of how molecular diagnostics, when integrated with molecular imaging and other data sets, is giving clinicians powerful new insights for making diagnoses, identifying appropriate therapies, and monitoring patient progress.

Register today and guarantee your place at this important event for pathology and radiology! The full agenda and speaker line-up for Molecular Summit 2009 on February 10-11 can be viewed here (or paste this URL into your browser: http://www.molecular-summit.com/program.htm )

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