The Impact of Global Clinical Development Japanese Perspective

1
The Impact of Global Clinical Development -
Japanese Perspective -

• IFPMA Asian Regulatory Conference 2008
• March 12, 2008
• Toshiyoshi Tominaga Ph. D.
• International Planning Director
• MHLW

2
Drug Lag Avg. Marketing Delay (2004)
Market Size (2006)


1,500

Japan 10
Rest of World 17
1.5 Yrs Development
2.5 Yrs

1,000
Europe 28
45
1.0 Yrs NDA Review
day
1,417

500
N. America
France 5
Germany 5
505
Average Time from Worlds 1st on 88 Top Selling
Drugs
Total 643billion
(Ref.IMS World Review)
(Ref. JPMA Research Paper 31 (2006))
3
Global Development and Drug Lags

• Drug Lags
• Slow Development Slow NDA Review
• Bad for Patients, Industry, Medical Sciences
• Simultaneous Global Development
• Ethnic Factors necessitate Japanese Cases but
  Refinement in Policies considered
• Bridging Studies cannot eliminate Lags
• Improvement in Clinical Trial Environment to
  increase Japans participation

4
Strengthening PMDA

• NDA Reviewers (doing also Consul.)
• Ca.200 (March 07)
• Ca.440 (March 10)
• Clinical Trials Consultations
• Fast Track for Global Development
• Increase 300 (06) to 1,200 (by March 12 )
• Waiting Period 3 mo. to 2 mo. (by March 09)
• Guideline (with MHLW)
• Basic Principles on Global Clinical Trials
  (Sep. 07)

5
Clinical Trials Activation 5-Year Plan (2007-2011)
Networking of Trial Sites
Budget 1.75 billion Yen (FY2007)
Doctors Incentive Infrastructure CRCs,
IRB Efficiency EDC
General Promotion on Subjects Information,
Incentive
6
Amending Japans GCP by March 2008
Japan GCP is ICH-GCP based but small Divergences
causing Difficulties

• Rules on IRB relaxed, more transparent
• Periodical Safety Update (/6 mo.) introduced
• Essential Documents reduced
• Registration Substance Delivery easier

7
Ethnic Differences

• Approved Doses
• Capecitabine (anti-cancer)
• 1,657 (Japan), 2,500 (EU/USA) mg/m2/day
• Telithromycin (antibiotics)
• 600 (Japan), 800 (EU/USA) mg/day
• 2. Reported ADR Incidences
• leflunomide (anti-rheumatis)
• interstitial pneumonia (JapangtUSA/EU)
• Irinotecan (anti-cancer)
• diarrhea (JapangtUSA/EU)

Unforeseeable with current Science
Currently
Japanese Clinical Data (basically) Necessary
Future
Refinement esp. about Asian Popns?
8
Health Ministers Joint Statement among China,
Korea Japan (April 8, 2007)

• Pandemic Influenza
• 2. Other issues
• Clinical Researches
• Emergency Preparedness
• Traditional Medicines

9
Tripartite Cooperation to study Ethnic Factors

PK Data
Clinical Data
Clinical Data
Dose ADR
Clinical Data
If Ethnic Factors are small, Data from 3
Countries can be combined and analyzed for
quicker Delivery of Drugs in the Countries
10
MHLWs Study Group on Ethnic Factors (August
2007-)

• Head Researcher
• Dr. M. Tohkin (National Institute of Health
  Sciences)
• Participating Organization
• NIHS, PMDA, JPMA, Academia, Japan CRO Assocn.
• Initial Working Question
• Drugs with Ethnic Difference b/w Caucasian
  Asians show Difference among the 3 Popns ?
• Tentative Findings
• Not as much RETROSPECTIVE (PK/PD) Data as
  expected
• Literature-based Comparison going on
• Abundant PROSPECTIVE DATA coming ?
• Future
• Cooperation with Chinese Korean Counterparts (?)

11
Hopeful Signs
No more
Slow
Costly
Over-quality
12
Japans Clinical Trials Increasing (?)
New GCP ICH E5
3-Year Plan
Total Registrations
?
1st. Registration
04 05 06
(MHLW)
13
Speed of Case EnrollmentEly Lillys Tadalafil
(Phase ?) 2005 2007
Cases / Site / Month

0.43
0.42
0.34
Total Cases 406 (Japan 26 ), 10 Countries, 83
Sites (12 in Japan)
By Courtesy of Eli Lilly Japan
14
Speed of Case EnrollmentAstraZenecas Vandetanib
(Phase III)
25 Countries, 221 Sites (Japan26)
No. of Randomization
May 06 July Sept. Nov. Jan.
07 Mar. May July Aug.07
By Courtesy of AstraZeneca Japan