Pharmacogenomics Enters the Japanese Market

This is a very exciting time in the drug discovery arena and specifically in the area of personalized medicine. It has been said that pharmacogenomics will change the landscape of how we use medicine to heal people.

Michæl Murphy

The pharmaceutical industry appears to be closer than ever to conducting clinical trials using pharmacogenomic technology. There is mounting evidence that individuals and even ethnic groups are not all affected by drugs in the same way. Predicting an individual's response to drug therapy offers the prospect of less risk to the public with better assurance for safer and more efficacious drugs.

In the following discussion, Michael Murphy of Gentris Corporation (Morrisville, NC), a global provider of pharmacogenomics services, responds to several questions about the pharmacogenomics market and his company's recent expansion into Japan.

Q. Congratulations on your partnership with FALCO biosystems and the formation of Gentris Japan. This is an interesting partnership, with Gentris a provider of applied clinical pharmacogenomic services and diagnostic product solutions, and FALCO a well-known Japanese medical testing laboratory. Can you give us some background as to how and why this relationship came about?

A. We were introduced to FALCO by one of our Japanese board members. We were looking for an established genotyping reference laboratory and FALCO has the best industry reputation in Japan.

Q. Why did Gentris choose to go to Japan first for its international expansion?

A. Gentris is the largest provider of pharmacogenomic testing to companies based in Japan. Currently we have eight large Japanese clients working in the United States and elsewhere. When we asked all of our clients where we should expand internationally, they chose Japan almost unanimously.

Q. Why is it so important that a good laboratory practice (GLP)-compliant pharmacogenomics laboratory be established in Japan?

A. Often the use of pharmacogenomic data in the future is not known. Data obtained under non-GLP compliance would likely not be acceptable to MHLW (equivalent of U.S. FDA in Japan). In addition, the underlying quality assurance incorporated into GLP regulations means that Gentris will provide clients the assurance that the data is robust and reproducible.

Q. It has been stated that there is a relationship between individual genetic differences and how a drug is metabolized. Has this clearly been identified in the Japanese culture? Can you give us some examples of the research that has been conducted?

A. It is well established that the genetics behind drug metabolism differs depending on the population that is being studied. For example, Japanese patients more frequently have a mutation in the EGFR (epidermal growth factor receptor) gene, and this can lead to a significant increase in adverse events for patients being treated with Iressa (gefitinib) for non-small cell lung cancer.

Q. What kind of standards does the Japanese counterpart to the FDA, the MHLW, apply to genetic testing and how does this affect Gentris Japan?

A. Currently MHLW has only advised pharmaceutical companies to "register" voluntarily the clinical programs in which pharmacogenomic testing (PGx) might occur, either prospectively or retrospectively. While the Japanese government is encouraging companies to obtain clinical samples for future testing, they have stated publicly that their guidance document on pharmacogenomic data submission will not be released until 2010.

Gentris Japan is well equipped to assist Japanese pharmaceutical companies build their biologic repositories (DNA banking) and navigate the path toward gene-based clinical trials following the FDA's Pharmacogenomic Data Submission guidance, which is viewed by most in the industry as a precedent for others to follow.

MHLW's proposed 2010 date for PGx guidance may cause Japanese companies to take a "wait and see" attitude, thus slowing adoption and use of Gentris Japan as the outsourced provider of PGx services. At the same time, it means that Gentris Japan will be well-placed when Japanese companies move forward in earnest with PGx. It also means they will increasingly look to the FDA for standards by which PGx studies are conducted. With Gentris Japan adhering to GLP standards that are promulgated and accepted by the FDA, the company could potentially be accepted as the de facto provider for PGx in Japan.

Q. Does the recent FDA regulatory guidance for the new type of medical test, IVDMIAs, affect the work you are doing?

A. No. This draft guidance, if ever accepted and finalized, will only affect clinical diagnostic laboratories that perform physician-referred testing.

Q. How many clinical trials in Japan are presently using PGx technology? Do you think PGx technology will lead to an increase in the number of trials in Japan?

A. We believe there are very few clinical trials using pharmacogenomics in Japan. Access to GLP genotyping established under the FDA's regulations (21 CFR 58) should accelerate incorporation of pharmacogenomics into clinical trials in Japan. Both foreign and domestic companies in Japan have been considering the use of pharmacogenomics because most have been doing these kinds of studies for many years in the United States and Europe.

Michael Murphy, President and CEO, Gentris Corporation

—Toby Jane Hindin, EdD, Editor-in-Chief, ACT