Companion diagnostics holds great promise for advancing the field of personalized medicine by allowing drug developers to identify subpopulations of patients likely to respond favorably or to experience unfavorable side effects from a drug or therapy.

But progress in the field has been slower than desired. There are several reasons for this, including the lack of evidence supporting the clinical usefulness of many current diagnostic tests, ongoing challenges in discovering and validating new biomarkers, reluctance on the part of Medicare and private payers to pay for diagnostic tests, and issues within the U.S. Food and Drug Administration’s (FDA) review and approval processes.

“Despite a few success stories, pharmacogenomics—research that explores ways in which genetic variations can be used to predict whether and how an individual patient may respond to a drug—has had limited impact to date on clinical practice,” said Joshua Cohen, PhD, senior research fellow at the Tufts Center for the Study of Drug Development (CSDD) at Tufts University, Boston. “Without clinically useful diagnostics, development of personalized medicine is likely to continue at a relatively slow pace,” he said.

Cohen is the author of CSDD’s July-August 2011 Impact Report, which identified and analyzed barriers to advances in companion diagnostics. Currently, less than 1% of all marketed drugs in the United States have a companion diagnostic, typically an in vitro test or device. And only 10% of marketed drugs carry any type of pharmacogenomics information on the label, according to the report.

Pharmacogenomics specialists surveyed for the report noted that many insurance payers remain skeptical about the usefulness and efficacy of companion diagnostics, and only a minority of payers require documentation that a diagnostic test has been conducted prior to prescribing. Even when a diagnostic test is included on the label, payers often will not pay for the test or require high cost-sharing.

Cohen conducted a formulary review of 21 leading Medicare Part D prescription drug plans covering about 80% of beneficiaries enrolled in the program. He found that reimbursement was at the discretion of each payer for five self-administered drugs having companion diagnostics—Gleevec (Novartis), Iressa (AstraZeneca), Tarceva (Astellas Pharma US/Roche/Genentech), and generics warfarin and abacavir.

An analysis of these drugs and three others—Erbitux (ImClone/Eli Lilly), Herceptin (Roche/Genentech), and Camptosar (Pfizer)—found that Iressa presents the highest barriers to developers and payers, followed by Tarceva, Erbitux, and Camptosar due to lack of coverage of companion diagnostics and high cost-sharing.

Signs of progress
For these reasons, experts predict only moderate growth over the next five years in post hoc development of companion diagnostics for already approved drugs and for co-development with new drugs. Despite this tepid outlook, there are ongoing signs of progress.

In June, the FDA approved a new genetic test to determine if women with metastatic breast cancer are HER-2-positive and, therefore, candidates for Herceptin (trastuzumab, Roche/Genentech). The test, called Inform Dual ISH (Ventana Medical Systems, Tucson, Ariz., part of the Roche Group), allows lab personnel to more easily count the number of copies of HER-2 genes in a small tissue sample using a standard, rather than fluorescence, microscope. Patients with more than the normal number of copies of the gene are likely candidates for Herceptin therapy. Herceptin is less effective and may cause severe adverse effects in those with the normal number of HER-2 genes.

In July, the FDA issued draft regulatory guidance on development of companion diagnostics. Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health, said that new genetic tests are making it increasingly possible to better target drugs “so that we’ll get the right drug to the right person at the right time.” One of the challenges, he added, “is how we regulate this new world of personalized medicine.”

The proposed guidance was published July 14, 2011 with a 60-day public comment window. “FDA is clarifying relevant policies related to these devices and products,” the guidance document states. “FDA is also developing appropriate internal policies and procedures to ensure effective communication among the relevant centers and to promote consistent and efficient product review.”

The agency notes that “ideally” a new drug or therapy and its corresponding companion diagnostic device would be developed contemporaneously “with clinical performance and clinical significance of the IVD diagnostic device established using data from the clinical development program of the corresponding therapeutic product.” But the FDA acknowledged that “there may be cases when contemporaneous development may not be possible.”

In those cases, FDA could expedite review of a new drug or therapy, absent a companion diagnostic, when the therapy is intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment exists. The agency might also consider revising an existing drug label to include an unapproved or uncleared test or diagnostic if the benefits “are so pronounced as to outweigh the risks from the lack of an approved or cleared IVD companion diagnostic device.”
The new guidance does not provide details on the kind or conduct of clinical trials needed to review co-development of therapies and companion diagnostics. It does, however, recommend that sponsors “consult early with FDA on the likely regulatory pathway” for companion diagnostic devices, but does not suggest a timeline.

Meanwhile, drug makers are continuing to partner with or acquire diagnostics companies. For instance, in July, Roche’s Ventana Medical Systems acquired MTM Laboratories AG (Heidelberg, Germany), a manufacturer of in vitro diagnostics for early detection of cervical cancer. Roche says the acquisition will complement its human papilloma virus assay for cervical cancer screening.

About the Author
Contributing editor Ted Agres, MBA, is a veteran science writer in Washington, DC. He writes frequently about the policy, politics, and business aspects of life sciences.