23
Sang-Goo Shin, MD President, Korea National Enterprise for Clinical Trials f fC Professor of Clinical Pharmacology Seoul National University Hospital & School of Medicine
Sang-Goo Shin, MDPresident, Korea National Enterprise for Clinical Trials
f f CProfessor of Clinical PharmacologySeoul National University Hospital & School of Medicine
St t f d d l t ti iti i KStatus of new drug development activities in Korean domestic pharmaceutical industries
Changing trends of clinical trials in Korea through 2000s. Activities for globalization in clinical trials in various sectors of Koreavarious sectors of Korea.Changing pattern of involvement in global trials : recognition of Korea staatus quorecognition of Korea, staatus quoKoNECT as a new initiatives for globalization
Asian collaboration in clinical drug development and expectation on recent Japanese changesexpectation on recent Japanese changes
KFDA USFDACompany Name Class KFDA Approval
USFDA Approval
SK Sunpla® inj* Anticancer drug (Gastric cancer) Jul, 1999
Daewoong Easyef® (EGF soln) Ulcer remedy for diabetic foot May 2001Daewoong Easyef® (EGF soln) Ulcer remedy for diabetic foot May, 2001
SK Joins® (SKI306X) T* Arthritis treatment Jul, 2001
Dong Hwa Milican® Inj Anticancer drug (Hepatoma) Jul, 2001
Joongwae Quroxin® Tab Antibacterial agent Dec, 2001
Dong A Stillen® Tab* Gastritis treatment Jun, 2002
LG Biotech Factive® Tab** Antibacterial agent Dec, 2002 Apr, 2003
Chong Kun Dang Camtobell® Inj Anticancer drug Oct, 2003
YuYu Maxmabill® Osteoporosis Nov, 2004
Yuhan Revanex® Duodenal ulcer treatment Sep, 2005
DongA Zydena® Tab Erectile dysfunction Nov, 2005
Bukwang Levovir® Cap Chronic hepatitis B Nov, 2006
SK Chem Embix® Erectile dysfunction Jul, 2007SK Chem Embix® Erectile dysfunction Jul, 2007
Source: Korea Drug Research Association,2007
N b f R&D ItClassification Development Stage
Number of R&D ItemsChange (%)
Apr, 2007 Dec, 2004
Marketed 12 9+40
Li d 2 1
NCE/NME
Licensed 2 1
Clinical
Phase 3 11 7 +57
Phase 2 17 10 +70
Ph 1 16 13 +23Phase 1 16 13 +23
Subtotal 44 30 +47Preclinical 69 49 +41
Exploratory 50 23 +117
Modified New
New tech/formulation/combination/DDS 122 71 +72
Biotech (incl. cell therapy) 47 22 +114Modified New Drugs Bulk product 110 68 +62
Diagnostic agent 9 10 +10
Others (functional material/product) 11 11 +0
Total 473 294 +61
Source: Korea Drug Research Association
Changing Trends of Clinical Trials in Korea through 2000s
Local ( Domestic + Bridging ) Multinational Study Ref. KFDA, 2007
ICH meeting140 Bridging trials
134
147
100
120
97108
95
110ICH / GCP
140 g g134
80
100
75
90
61
IND / NDA Separation
Global Trials
40
6042
31 28 27
38
18 17
46
20
1998 1999 2000 2001 2002 2003 2004 2005 2006
5
18 17
2007
Regional CTC Program
Benchmarking Australian efforts : CTX, CTN
(a) The number of CTX applications, CTN trials, and the number ofsites under a CTN in Australia (1990~2000)
(b) National and Regional support for globalization
Clinical Trials - National Technology Roadmap
<Strength><Strength> <Weakness><Weakness>
1. 임상시험관련인원 부족
2002, MOST & MOHW
1. 제약의학의 태동 및 제약의사의 증가
2. [신기술 기반] 임상시험센터
3. 경쟁력 있는 연구자 집단
4. 다수의 임상시험수탁기관
2. 임상시험연구자 [GCP 등] 및 제약회사 경영진의
이해 부족
3. 임상시험계획승인 제도 비효율성-청내 기구편성
4. 국내 제약회사의 임상시험 기반에 대한 투자 미비다수의 임상시험수탁기관
5. 천연물 신약을 포함한 독점적 치료영역군
6. 상대적인 저가 의료수가 및 임상시험비용
5. 지역 및 국가 임상시험심사위원회의 부존
6. 영어를 이용한 의사소통의 어려움
7. 공인된 이상반응용어를 비롯한 임상시험관련
용어집의 미비
Expert Groups Recommend… global
communication, competitiveness
SWOT AnalysisSWOT Analysis
<Opportunity><Opportunity> <Threat><Threat>
communication, competitiveness
• Center of Excellence
f C f1. 국제적인 수준의 의료
2. ICH 기준을 비롯한 국제수준의
임상시험관련 기준의 조속한 도입
1. 임상시험시장으로서의 중국의 등장
2. 임상시험의 질과 윤리성에 대한 기대수준의
증가
<Opportunity><Opportunity> <Threat><Threat>• Training program for CT professionals• IRB International Accreditation
R l t l H i ti ICH임상시험관련 기준의 조속한 도입
3. 국내 질병의 서양화의 추세
4. 국제적인 조화를 이룬
임상시험관리기준
5 한국제약시장의 폭발적 성장
증가
3. 임상시험에 대한 국민의 부정적 태도
4. 급변하는 국제적인 관련 규정 및 기준
5. 의약품 등의 개발비의 폭발적 증가
제약업계의 고도 경쟁
• Regulatory early Harmanization on ICH……….
5. 한국제약시장의 폭발적 성장
6. 다국적 제약사에 의한 아시아 인종에
대한 임상시험의 증가
6. 제약업계의 고도 경쟁
Other Government Initiative; Streamlining of IND Review system
Reduced IND approval time in KoreaReduced IND approval time in Korea
140days KFDA database
100
120
140
60
80
100
40
60
20
1998 1999 2000 2001 2002 2003 2004 20051998 1999 2000 2001 2002 2003year
2004 2005
New RegulationsNew Regulations
Governmental Initiatives to Support Clinical Trials & Research
G t t d j t f• Government-supported projects for new drug candidate identification & development by MOST(1991-)
• Accreditation of Clinical study sites by KFDA (1995-)
Regional Clinical Trial Centers b• Regional Clinical Trial Centers by MOHW (2004-)- supporting ~ US$ 5 million per center
• Korea National Enterprise for clinical Trials (KoNECT): 2007. 12 – 6 years15 R i l Cli i l t i l t- 15 Regional Clinical trial centers
- Clinical trial related professionals Training Program, - New innovative technology supporting
• 2004 – 2 centers• 2005 – 4 centers• 2006 – 3 centers• 2008 – 3 centers• 2009 – 3 centers - New innovative technology supporting
program
KAIRB (2002- ) and,International Accreditation of IRBsInternational Accreditation of IRBs
• Samsung Medical Center IRB - AAHRPP June , 2006
• Seoul National Univ. Hosp. IRBs • Asan Medical Center IRBAsan Medical Center IRB
- SIDCER/FERCAP Dec., 2006• Inje University Busan Hospital IRB • Catholic University KangNam Hospital IRB• Chonnam University Hospital IRB
SIDCER/FERCAP 2007- SIDCER/FERCAP, 2007
2007 : KAIRB become formal Non-Profit Organization supporting/endorsed by MOHW, O g o suppo g/e do sed by O W,for national education of IRB professionals
- Periodic education workshops- 2 or 6 months fellowship training(10 per yr)
10
2 or 6 months fellowship training(10 per yr) in Western IRB, Seattle USA
250
300
218
281
150
200
f Stu
die
s
185
147134
100
150
Num
ber o
95 90108 110
0
50
Subtotal Multinational Domestic Subtotal Multinational Domestic Subtotal Multinational Domestic
2005 2006 2007Phase 1 36 2 34 68 5 63 57 7 50Phase 2 35 19 16 36 15 21 66 46 20Ph 3
0
Phase 3 106 68 38 105 81 24 133 93 40Phase 4 8 6 2 9 7 2 25 1 24
•• Prof. ByungProf. Byung--Hee OhHee OhCardiology, SNUH (Global PI of Aliskiren, Norvatis)
•• Prof. YoonProf. Yoon--Ku KangKu KangOncology, AMC (Global PI of Xeloda Phase III study in gastric cancer Roche)gastric cancer, Roche)
•• Prof. YoungProf. Young--Joo BangJoo BangOncology, SNUH (Global PI of Sunitinib Phase II study in gastric cancer, Pfizer)
•• Prof. SunProf. Sun--Young RaYoung RaOncology, YUMC (AP PI of Sunitinib Phase II study in renal cell carcinoma, Pfizer)
•• Prof SunProf Sun--Woo KimWoo KimProf. SunProf. Sun Woo KimWoo KimEndocrinology, SMC (Global PI of Vildagliptin, Phase III study in T2DM, Norvatis)
•• Dr. Jin Soo Lee Dr. Jin Soo Lee Oncology NCC (Global PI of Zactima ZD6474 Phase IIIOncology NCC (Global PI of Zactima ZD6474 Phase IIIOncology, NCC (Global PI of Zactima, ZD6474 Phase III Oncology, NCC (Global PI of Zactima, ZD6474 Phase III study for lung ca, AZ)study for lung ca, AZ)
•• Prof. Joon Soo Kwon, Prof. Joon Soo Kwon, Psychiatry, SNUH (Global PI of 11286 Sertindole, Phase Psychiatry, SNUH (Global PI of 11286 Sertindole, Phase III t d f hi h i L db k)III t d f hi h i L db k)III study for schizophrenia, Lundbeck)III study for schizophrenia, Lundbeck)
•• …………
Local vs Global in Asian Countries
250 Global
200
250 Global
Local
150
100
50
0
Global 7 12 17 18 37 71 73 90 118 131 136L l 1 2 214 1 63 8 12 10 50 22 15
Vietnam Parkistan Japan Indonesi
a China Singapore Thailand HK Korea Taiwan India
Local 1 2 214 1 63 8 12 10 50 22 15
Sources, Hong Kong Univ. CTC : www.clinicaltrials.gov (Oct06)
Top 5 Asian Emerging Cities
Sources, Hong Kong Univ. CTC : www.clinicaltrials.gov (Oct.06)
236250
No of sites in global trials
236
202200
250
154150
102 98100
50
0Seoul Taipei HongKong BangKok Singapore
Industry Sponsored Trials in Asia
Sources, GSK : www.clinicaltrials.gov (10JAN08)
456425
388450
500
388 378350
400
212 212188200
250
300
188
100
150
200
0
50
Japan Korea India TW Thai Singapore HKJapan Korea India TW Thai Singapore HK
NB ; Scope of CT - Sponsored CT (Ph1-IV)
Trends in the globalization of Clinical TrialsN R i /D di 2008 1 (2007 4)- Nature Review/Drug discovery 2008. 1 (2007. 4)
Governmental Initiatives to Support Clinical Trials & Research
G t t d j t f• Government-supported projects for new drug candidate identification & development by MOST(1991-)
• Accreditation of Clinical study sites by KFDA (1995-)
Regional Clinical Trial Centers b
• 2004 – 2 centers• 2005 – 4 centers• 2006 – 3 centers• 2008 – 3 centers• 2009 3 centers• Regional Clinical Trial Centers by
MOHW (2004-)- supporting ~ US$ 5 million per center
• 2009 – 3 centers
• Korea National Enterprise for clinical Trials (KoNECT): 2007. 12
R i l Cli i l t i l t- Regional Clinical trial centers- Clinical trial related professionals Training
program, - New innovative technology supporting
program
Korea National Enterprise for Clinical Trials (KoNECT)
2007. 12 – 6 years program
Clinical Trials (KoNECT)
2007. 12 6 years program
• RCTC : 15 Regional Clinical trial centers- 6 more CTC (2008, 2009)
• Clinical Trials Professional Training Academyy- 12 Center of Excellence in Education & Training- Clinical Investigators, Clinical Pharmacologist ;
(domestic/oversea)- CRA, CRC, CT Pharmacist- Pharmaceutical Medicine- Biostatistician, Pharmacovigillance, DB manager
• New innovative technology development & Propagation- 10 -15 Centers of Excellence in new10 15 Centers of Excellence in new
technology - 6 major technologies related critical path.
Company Target Diseases Country StatusA (J) Prevention of Venous
Thromboembolism (FactorJ/K/Ch/T/HK On-going
Thromboembolism (Factor Xa inhibitor)
S (JK) Type 2 DM (Insulin) J/K FinishedS (JK) Gastric Cancer J/K On-goingA (MN) Schizophrenia K/Ch/T (30 centers) On-goingM (JK) G t i C J/K (P I/II ) O iM (JK) Gastric Cancer J/K (P I/IIa) On-goingP (MN) Osteoporosis K/J/T FinishedP (MN) Smoking K/T FinishedP (MN) Smoking K/T FinishedP (MN) Overactive Bladder J/K FinishedH (K) Hypertension J/K On-going
Several recent examples of Asian Collaboration
New 5 Yearly Clinical Study Activation Plan, 2007Core Research Centers / MHW, Japan
National Cancer CenterNational Cancer Center
National Cardiovascular Center
N i l C f N l d P hiNational Center for Neurology and Psychiatry
International Medical Center of Japan
National Center for Child Health and Development
Chiba University Hospital Clinical Research Center
Oita University, Faculty of Medicine
Kitasato University, School of Medicine
Keio University, Center for Clinical Research
Center for Support and Education of Clinical ResearchCenter for Support and Education of Clinical Research
MOU (2007. 1. 29) of CCCP/KoNECT & J-ClipNetfor early phase study collaborationfor early phase study collaboration
CCCP /K NECT• CCCP /KoNECT (Core Center for Clinical Pharmacology):
- Seoul National University hospital
- Yonsei University Hospital
- Asan Medical Center
- Inje University HospitalInje University Hospital
• J-ClipNet (Japanese Clinical Pharmacology Network for Global Trials):
- Oita university hospital- Kitasato University East HospitalKitasato University East Hospital
- St. Marina University Hospital
- Showa University Hospital
H t U i it H it l- Hamamatsu University Hospital
- Ehime University Hospital
E h h h i hi f l b l i l i K i d• Even though short in history of global trials in Korea, industry-academia-government’s combined effort has produced an environment friendly to global clinical trials within a relatively short period of time.
• Good performance in late phase trials, in addition to excellent medical care facilities and investigators has led multinational pharma’s tocare, facilities and investigators, has led multinational pharma s to bring in earlier phases trials.
• New drug development by Korean domestic companies has started to gear up.
• We welcome the recent Japanese governmental policies• We welcome the recent Japanese governmental policies anouncing “New 5 year clinical study activation” and “shifting global attitude”, as a momentum of activation for Asian collaboration in clinical drug development in this region.
