Harry Glorikian Senior Executive, Board Director, Consultant, and Author

Genomic Testing Is Necessary to Identify the Right Patients for Treatment

In late May, the oncology market was riveted by the FDA’s approval of Keytruda (pembrolizumab) for adult and pediatric patients with any solid tumor with a specific biomarker referred to as microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR)1. Following that announcement, Loxo Pharmaceuticals became the media darling of the American Society of Clinical Oncology meeting, after sharing its preliminary results for larotrectinib (LOXO-101), a candidate for cancers with a different biomarker, TRK or NTRK fusions2. But for all the publicity and speculation about pharmaceutical companies expanding their R&D for “tumor-agnostic” drugs, the in vitro diagnostics (IVD) industry could be the real winner.

This point is supported by the title of an article in MIT Technology Review by Emily Mullin, “Promising New Cancer Drugs Won’t Go Far Unless Everyone Gets Genetic Testing”3. The article underscores the substantial barriers that remain for precision medicine, while simultaneously highlighting the tremendous opportunity for the IVD industry. To make targeted therapies work, genomic testing is necessary to identify the right patients for treatment. In patients without the “right” mutation, a targeted drug may be no better than a placebo, or worse yet, could lead to negative outcomes for patients due to serious side effects.

There are two main barriers to widespread adoption of genetic testing: Insurers refusing to pay for testing, which leaves patients shouldering the cost (or deciding not to have testing at all), and operational issues that keep doctors from being able to order the tests in a timely, efficient manner. The former issue is one the IVD industry has the potential to quickly change.

A variety of factors influence a payer’s coverage decision for diagnostic tests. These include existing clinical guidelines for the test, FDA approval status, competitors’ coverage determinations, and technical evidence assessments. For example, the CDC’s Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group, active from 2004-2014, used a framework that included analytical validity, clinical validity, and clinical utility4. Health technology assessments (HTAs), performed in-house or through third-party organizations, form the basis of evidence for coverage policy decisions. Understanding how they are performed and what data are desired is essential for IVD developers5. At the very least, HTAs will look for evidence supporting the analytical validity and clinical validity of a test.

Historically, manufacturers have kept those data private, preferring to present evidence as posters at scientific conferences, through narrowly-distributed white papers, or (mostly), not at all. In the early days of genetic testing, this type of proprietary information could be viewed as a competitive advantage. But over time, that has resulted in the overwhelming majority of HTAs finding a lack of published evidence to support the use of these tests. Consequently, payers continue to deny coverage for genetic and genomic testing, except for a few, well-characterized disorders, and express opinions that this testing remains “experimental” and “unproven.”

Without insurance reimbursement for these tests, the financial burden falls to the patients or to the manufacturers, who often heavily subsidize the tests. Neither is a long-term sustainable option.

How can we break this stalemate and take advantage of the tremendous opportunities in the era of precision medicine? Publish the data! This is essential and can be the difference between the IVD manufacturer that receives a positive coverage determination from insurers and one that doesn’t.

For developers still in the R&D phases, collecting the right data during design validation, where production-level devices capture the end-user experience, and in clinical trials should be a priority. For existing molecular diagnostics, retrospective analyses and/or registries can provide real-world evidence of the validity and utility of the test. These data, in turn, can serve as the basis for seeking regulatory approval for the IVD or to form the basis of evidence for HTAs.

The recent FDA PMA for Thermo Fisher Scientific’s Oncomine Dx Target Test is a case in point6. In an interview with MedCity News, Joydeep Goswami, president of clinical NGS for Thermo Fisher noted, “While we presented evidence of analytical validation of all the different genes, given the initial companion drugs were all non-small cell lung cancer-related, the FDA chose to initially limit this approval to that patient group,” but he said the manufacturer intends to work with the FDA to further expand the indications for which the test can be used, add genes to the panel, and expand its use with additional medications6. Manufacturers that can clearly show their assay is valid and has utility will more easily make the case for its inclusion in value-based care.

The Keytruda approval is a boon to the IVD industry, opening up more opportunities for assays that can better segment the patient population for the optimal treatment and supporting precision medicine. Importantly, the implications of this decision extend beyond oncology indications. Publishing the key data that insurers will ultimately use to make coverage decisions will be a substantial part of making precision medicine a reality for more patients. 

Harry Glorikian ([email protected]) is a senior executive, board director, consultant, and author in the life sciences/healthcare industry.

1. FDA, U.S. Dept. of Health & Human Services, 2017.
2. M. Herper, "A New Cancer Drug Helped Almost Everyone Who Took It. Almost. Here's What It Teaches Us," Forbes, (June 3, 2017).
3. E. Mullin, "Promising Nnew Ccancer Ddrugs Wwon’t Ggo Ffar Uunless Eeveryone Ggets Ggenetic Ttesting," MIT Technology Review (June 6, 2017).
4. S. M. Teutsch et al., The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group. Genetics in medicine : official journal of the American College of Medical Genetics 11, 3–14 (2009).
5. H. Glorikian, Commercializing Novel IVDs: A Comprehensive Manual for Success.  (Insight Pharma Reports, Needham, MA, 2017).
6. J. Preston, "Another Win for Precision Medicine: FDA Approves Companion Diagnostic Panel," MedCity News, (June 23, 2017).

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