Must Have vs. Nice-to-Have: Navigating Complementary and Companion Diagnostics Tests

We recently viewed the excellent Diagnostics Market Association webinar on Companion vs. Complementary Diagnostics.   The distinction between "must perform" tests required before prescribing a drug and the "nice to have" type tests, if you will, to enhance efficacy, is a subject worthy of attention, one that we explored in our recent market research study on the companion diagnostics market segment, authored by Sannes & Associates.  

"Must Have"s & "Nice To Have"s in the Diagnostics Industry

The story of how companion diagnostic approaches developed will not be news to most. The traditional approach to drug development was “one size fits all patients.”  However, it is now known that not all patients who have been diagnosed with a particular disease will respond in the same way to a drug that was developed to treat that disease.  The drug may not work in all patients, and some patients may develop adverse side effects to the drug.  There was a need to be able to predict, before a drug is administered, which patients are likely to benefit from use of that drug, which patients will not benefit, and also which patients may be harmed if they are given the drug.   Enter companion diagnostics.  It is possible for some diseases and some therapeutic solutions, to develop drugs that are targeted towards specific molecular changes that have occurred.  These drugs can be very effective, but only for those patients who have the molecular changes being targeted. Thus a companion diagnostic test is developed and the test must be performed per drug label.  Already, several such diagnostic tests are developed and approved by the FDA.  

But here is what is somewhat new.  Companion status is not the only situation where a test can improve the usage of a therapeutic.  "Complementary diagnostics” is a relatively new term that has been introduced by the FDA.  Slides from a November 2015 presentation by the FDA indicate that complementary diagnostics are “Diagnostics that are not required but provide significant information about use of a drug.”  This same slide also indicates that a writing group (for a complementary diagnostics guidance) was forming.   

The most recent example of a new drug and complementary diagnostic test combination is Roche’s Tecentriq (atezolizumab) for treatment of urothelial carcinoma, a common type of bladder cancer.  The FDA also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumor-infiltrating immune cells and help physicians determine which patients may benefit most from treatment with Tecentriq.   In October 2015, Dako announced that the FDA had approved a new companion diagnostic assay that can reveal whether a patient with advanced non-small cell lung cancer (NSCLC) is likely to respond to a new form of treatment.   This test is PD-L1 IHC 22C3 pharmDx, which was developed in partnership with Merck & Co., Inc. (known as MSD outside the U.S. and Canada), which developed the anti-PD-1 therapy KEYTRUDA® (pembrolizumab).   Several examples of complementary diagnostic tests have been approved by the FDA are detailed in our report. 

Complementary and Companion Diagnostic Tests 

The DxMA webinar had a few key takeaways.  For one, that there was no clarity yet on complementary versus companion diagnostics rules of the game, and the diagnostic industry 'real world' view is that the regulatory solution is confusing, possibly underlying rationale to increase evidence hurdles for new therapy enabling testing, and several other points.  This certainly reflects a common diagnostic industry perspective well, and some of the challenges that diagnostic test makers face when navigating the companion and complementary diagnostic development process.  Compared to a traditional test product, the process can be confusing.  

We do think the concept of a companion diagnostic test is best understood in this way - the process is driven by pharmaceutical companies with either the direct participation (through partnership) or the indirect participation (launching a similar test to a marketed and approved one) of the diagnostic companies.   The first priority for pharmaceutical companies is to develop and commercialize their drugs.  Diagnostic tests are tools to help do this.  The pharmaceutical companies determine whether or not a companion diagnostic test is essential to identify patients for clinical trials during drug development, and thus also essential for approval of a new therapy.  The decision of whether a test is a companion diagnostic test or a complementary diagnostic test is driven by how pharmaceutical companies design their clinical trials, and whether or not a test is essential or provides information that is useful but not essential for safe and effective use of a drug.

 It is possible that safety or efficacy issues relating to a subpopulation of patients is not known until late in the development of a therapy, or until after the therapy is approved an on the market.  If/when this happens, a companion diagnostic may be developed and approved after the therapy is on the market.  However, the need for this diagnostic test is driven by medical issues, and it's not likely in our view that the primary reasoning is barrier to test but rather to be sure right drug for patient is observed or another therapy is chosen.  

There is less clarity for complementary diagnostic tests that provide information that is important and nice to have, but not essential.  But there is some, and it likely involves data and proof.  There must be reasons to use these tests before they will be adopted.  For test makers adjusted to the FDA approval process, the payor reimbursement approval might be more arduous and require resources and planning.   For example, oncology personalized medicine tests is a very crowded and highly competitive field in which a large number of diagnostic companies (including many companies offering services via their own CLIA-certified laboratory) offer many tests and panels of tests for “actionable” biomarkers that have been validated in the scientific literature, or offer genetic signature tests (such as Genomic Health’s Oncotype tests) that have been validated with clinical studies that have also been published in the scientific literature.  There are even more emerging diagnostic companies that offer tests and services that may not have the same depth or amount of published data validating their products or services.   Given the actions of myriad competitors in the market, the best data will put companies in a good position to succeed.  IVD companies should understand and embrace the need to develop clinical studies and resulting data as part of their product development or risk not fully participating in the complementary drug opportunity. 

 Our report, Companion Diagnostics Markets, details scores of projects and hundreds of companies in the market. It also forecasts opportunity market sizes for the overall combined companion and complementary testing market.  The report can be found at