The Present Situation of PGx/PGt Study in Japan - JHSF Questionnaire Survey - Daiichi Pharmaceutical Co., Ltd. Osamu Sato Ph.D.

Tackling of JHSF JHSF (Japan Health Sciences Foundation) was established by 128 companies in April, 1986, under the support of the MHLW (MHW at that time) JHSF (Japan Health Sciences Foundation) was established by 128 companies in April, 1986, under the support of the MHLW (MHW at that time) The mission of JHSF is promoting of basic and advanced technologies related to medicine, drugs and of contributing to human health and welfare The mission of JHSF is promoting of basic and advanced technologies related to medicine, drugs and of contributing to human health and welfare Since 1998, JHSF has continuously performed the investigation of the tendencies and future views of genome sciences and has offered reports every year Since 1998, JHSF has continuously performed the investigation of the tendencies and future views of genome sciences and has offered reports every year In the report for 2002 JHSF performed a questionnaire survey in order to know the present situation of PGx/PGt in Japan In the report for 2002 JHSF performed a questionnaire survey in order to know the present situation of PGx/PGt in Japan

JHSF Questionnaire Survey Purpose: Grasp of the PGx/PGt Present Situation in Japan Purpose: Grasp of the PGx/PGt Present Situation in Japan Term: September 27 to November 1, 2002 Term: September 27 to November 1, 2002 Target: 91 JHSF Member Companies Target: 91 JHSF Member Companies Method: Questionnaire Survey by Mail Method: Questionnaire Survey by Mail Recovery: 53 Companies(44 valid) Recovery: 53 Companies(44 valid) Breakdown of the 44 companies: Breakdown of the 44 companies: 37 Pharmaceuticals and 7 Others

Questionnaire Items 1. Study of a relationship between developing drugs and gene polymorphism 2. Problems related to ethics in PGx/PGt studies 3. Problems related to the method of PGx/PGt study 4. Problems on application using the results of PGx/PGt studies 5. Post-marketing PGx/PGt study 6. Problems related to the marketing of PGx/PGt-related drugs etc.

1. Do you have any plans to conduct PGx/PGt study with developing drugs ? Studies conducting or scheduled to be conducted in 2 or 3 years : conducting : scheduled Yes 37 ％ No 63 ％ （ n=43 ） （ n=10 ）

Reason of “No” （ n=33 ） （ n=39 ） Objectives （ n=5 ） Adverse Reaction Respnder/Non-Responder Exclusive Intention Others Yes 13 ％ No 87 ％ Cost Effectiveness Difficulty in Collaboration with Institution Difficulty in getting IC No Proper Drug Others 2. Do you have any plans to conduct PGx/PGt study with post-marketing drugs ?

3. What do you think about the necessity of guidelines for conducting PGx/PGt studies ? Not necessary 5% Necessary85% Not familiar with this problem 10% Total 9.84 Not familiar with this problem 4.92 Not necessary Necessary ％Replies （ n=41 ）

Not familiar with this problem 21%(8) （ n=39 ） Replies from 24 companies 8.32Other Patients may not accept gene testing Objection from the sales division Patients may prefer less effective drugs prescribed without gene testing A higher price, which compensate the decrease in the number of patients, may not be accepted. ％Replies 4. Are you concerned about decreases in the patients number by PGx/PGt study ? Yes 66 ％ (26) No 13 ％ (5)

Orphan-development Financial support Registration without Phase III Premium NHI price No idea Others （ n=38 ） 5. What do you expect for MHLW if you will develop drugs for the non-responders ? develop drugs for the non-responders ?

Summary of the Survey Difficulties in finding appropriate methodologies Difficulties in finding appropriate methodologies Not clear relationship between GCP and “Common Ethical Guideline” Not clear relationship between GCP and “Common Ethical Guideline” Decreased number of patients Decreased number of patients Preparation of new ethical guideline for PGx/PGt Preparation of new ethical guideline for PGx/PGt Establishment of system to conduct retrospective PGx/PGt study Establishment of system to conduct retrospective PGx/PGt study Premium addition on regular NHI price Premium addition on regular NHI price