The global market for personalized medical treatment is growing, and the companion diagnostics market is no exception. Western companies offering companion in vitro diagnostic (IVD) tests are growing in Japan, where regulators, physicians, and patients alike are primed to make drug therapies more effective.

Companion diagnostics are IVD devices that help doctors decide which specific drug treatments to offer patients and what dosages to prescribe. They are tailored specifically to each individual patient. A patient may have a genetic mutation, for example, that makes a certain drug therapy more or less effective. Companion diagnostic tests can determine whether the drug in question is likely to benefit that patient. Companion diagnostics are rapidly becoming more advanced as scientists make strides in understanding the complex nature of diseases.

Oncology is one field where companion diagnostic tests are experiencing particularly rapid growth, as they have been critical to the success of many cancer therapies. As the tests become more sophisticated, their range of use is broadening.

Key Companion Diagnostics Regulations in Japan

The Japanese agency responsible for the regulatory oversight of companion diagnostics is the Pharmaceuticals and Medical Devices Agency (PMDA), which is under the Ministry of Health, Labor and Welfare (MHLW). Because companion diagnostic tests are designed to be paired with a specific drug, regulations require close collaboration between experts evaluating the tests and those evaluating pharmaceuticals.

The PMDA defines companion diagnostics as in vitro or therapeutic products used to identify patients who are:

1. Expected to respond better to a specific therapeutic product
2. Likely to be at a high risk of developing adverse events associated with a particular therapeutic product
3. Would benefit from the optimizing of the treatment in regards to dose, schedule, or discontinuation of a particular therapeutic product.

Examples of companion diagnostics, according to the PMDA, may include in vitro diagnostics used for biochemical assays related to organ functions such as creatinine, transaminases and blood glucose levels, as well as tests used to identify a disease, check a treatment effect, or assist in follow-up observation.

Requirements to register a companion diagnostic product are essentially the same in Japan as those for general IVDs. But the drug company and the companion diagnostic company are required to collaborate and to apply for approval of the diagnostic around the same time as the application for the approval of the corresponding drug.

In their approval applications, companion diagnostic manufacturers must detail the product’s intended use, active ingredients, manufacture method, storage condition, shelf life and quality control, among other information. Attached data must include materials such as the product development history, conformity to essential requirements, risk analysis and clinical performance (if it is a new test).

To determine the best regulatory path, applicants are encouraged to schedule a formal consultation with PMDA officials, although a fee is charged for these consultation meetings. Fees normally range from $265 for a preparatory meeting to upwards of $7,300 for an evaluation of clinical studies. The total review time ranges from 4 to 12 months on average. At the meetings, applicants submit data on the development status of the drug, an outline of the companion diagnostic product’s specifications, foreign clinical data, and other related materials. There are different types of consultations, including consultations that are focused on the pre-development stage of the companion diagnostic, the protocol of a clinical study, evaluation of data from a clinical study, and more.

Western Companion Diagnostics Developers Look to Japan

Companion diagnostics firms making forays into the Japanese market include Qiagen, Invivoscribe, Myriad, Foundation Medicine and NanoString technologies.

In January 2018, NanoString Technologies, an IVD company in Seattle, Washington announced it had struck an agreement with Riken Genesis of Kawasaki, Japan to seek approval of its companion diagnostic test, the nCounter DX LymphMark. The diagnostic is designed to help identify treatment options for Diffuse Large B-cell Lymphoma patients.

In March 2018, Foundation Medicine, based in Cambridge, Massachusetts, announced it was pairing its comprehensive genomic profiling services with Chugai Pharmaceutical, based in Tokyo. Chugai has submitted a request to the MHLW for regulatory approval of Foundation Medicine’s FoundationOne CDx, a companion diagnostic test for detecting solid tumors.

In April 2018, Myriad Genetic Laboratories, based in Salt Lake City, Utah, received approval from the MHLW to market and manufacture its BRACAnalysis Diagnostic System, a companion diagnostic for breast cancer patients. The system is used to test the PARP inhibitor, Lynparza, marketed by AstraZeneca (Cambridge, United Kingdom) and Merck Laboratories (Kenilworth, New Jersey). Lynparza treats patients with BRCA-mutated metastatic breast cancer.

In May 2018, San Diego, California-based Invivoscribe also made a move into Japan, submitting an application to the PMDA for its companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay. The product is designed to detect mutated genes in genomic DNA from acute myeloid leukemia patients.

And finally, in August 2018, Qiagen, a molecular diagnostics firm based in Hilden, Germany, announced a collaboration with Japan’s largest clinical laboratory testing firm, Tokyo-based SRL. Under the agreement between the two firms, companion diagnostic products from Qiagen will be used to test new drugs being developed by SRL to treat leukemia and other cancers. The companion diagnostic products include next-generation sequencing and real-time polymerase chain reaction solutions.

More and more Western companion diagnostics firms are interested in, and expanding in, the promising Japan market. Able to route patients suffering from a host of diseases to therapies that work best for their specific genetic makeup and cause less side effects, the use of companion diagnostic products will continue to increase in Japan.