Jean Pierre Paccioni, EIPG President Presentation at EIPG – BIPA Symposium “Clinical Trials Research” at the Faculty of Pharmacy, Medical University of Sofia, Sofia 2014.

1. PharmacistPharmacist
Industrial Vision of Clinical trialsIndustrial Vision of Clinical trials
Vision of International Clinical Research
(Leem Study)
JP PACCIONI EIPG April 11th, 2014

2. Pharmacist Industrial Vision of Clinical trials
 Clinical Trials are by definition the only way to get
Marketing Authorization Approval of a new Marketing Authorization Approval of a new
Medecine
B Cli i l T i l f l  But Clinical Trials are a part of a long
Pharmaceutical Process from Research and
D l l d l hDevelopment… to approval and launch
 8 to 12 years process
 A very complex process – 1 molecule on 10 000
 A costly process : 1 to 1,5B$ for a new Entity
 A risky process : how to finance R&D with a limited
number of marketed medecines
JP PACCIONI EIPG April 11th, 2014

3. Pharmacist Industrial Vision of Clinical trials
NEW DRUG
APPROVAL
LAUNCH
Price
PV
GCP
Safety
Tolerance/Efficacy
Pivotal studies
CLINICAL TRIALS
Phase 3 – MULTICENTRIC
Phase 2 – INTERNATIONAL
Ph DEVELOPMENT
Regulatory Affairs
reports
Pivotal studies
Phase 1 – DEVELOPMENT
CT submission
traceability
Non Human Studies
Toxicity
Pharmacology
Pharmacokinetic
reports CT
Packaging/Randomization
GLP
NEW ENTITY
Pharmacokinetic
Metabolism
PRODUCTION
CAPACITY
Manufacturing site
Stability
Batch release
NEW ENTITY
Pilot Batch
Production
Stability
GMPreports
Research
Galenic
formulation
8-12 years

4. Pharmacist Industrial Vision of Clinical trials
 A lot of candidatesRESEARCH
very few Products to Launch10 000 candidates
PRE‐CLINICAL
100 candidates
CLINICAL TRIALS
10 l l10 molecules
LAUNCH/PV
JP PACCIONI EIPG April 11th, 2014 1 product

5. INTERNATIONAL CLINICAL RESEARCHINTERNATIONAL CLINICAL RESEARCH
Synthesis of 6 surveys conducted by Leem
since 2002 and 2012
5

6. Clinical Research: a major issue for French attractiveness
within an increasingly competitive environmentwithin an increasingly competitive environment
 Survey performed by the Leem every 2 years in association with
P bli i H lth C lti t d t it ti l i fPublicis Healthcare Consulting to conduct a situation analysis of
France’s position in international clinical research (quantitative
aspects and qualitative perception)
 Exceptional and unique scope of available data in Europe thanks
to 6 surveys conducted since 2002to 6 surveys conducted since 2002
 International studies of development (Phase II et III)
with French participation
Since 2004, nearly 500 studies, over 1
million patients included
6
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

7. The survey representativeness increased steadily between
380%
y p y
2002 and 2012 to reach 30 laboratories
Evolution of participation in the survey between 2002 and
2012
61% 62%
72%
68%
29 30 30
35
70%
80%
et
atingin
2012
44%
36%
20
19 20
25
50%
60%
enchmarke
esparticipa
rvey
36%
11
10 10
15
30%
40%
eoftheFre
ofcompanie
thesur
10
5
10
10%
20%
Share
Numbero
00%
2002 2004 2006 2008 2010 2012
The survey 2012 only contains qualitative data
7
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

8. 2012 survey: a significant sample2012 survey: a significant sample
30 pharmaceutical companies involved in the 2012 survey
• Daiichi-Sankyo
• Gilead
• GlaxoSmithKline
• Abbott
• Actelion
• Amgen
• MSD
• Novartis
• NovoNordisk
For France
• 559 studies (vs 415 en 2010) Of• GlaxoSmithKline
• Ipsen
• Janssen
• Léo Pharma
• LFB
• Amgen
• Astellas
• AstraZeneca
• Bayer
• Biogen
• NovoNordisk
• Pfizer
• Pierre Fabre
• Roche
• Sanofi
( )
which 110 studies de phases I et I/II
• 22 114 patients (vs 22 095 en 2010)
3 152 t ( 2 433 2010)• LFB
• Lilly
• Lundbeck
• Merck Serono
• Biogen
• BMS
• Boehringer
Ingelheim
• Celgene
• Sanofi
• Sanofi Pasteur
• SPMSD
• Takeda
• 3 152 centers (vs 2 433 en 2010)
For international comparison
New participants : Companies that have not participated to the previous surveys
• Celgene For international comparison
• 420 studies (vs 328 en 2010)
• 246 895 patients (vs 249 704 en
Note : Loss of 3 laboratories : Cephalon, Cytheris, Servier
d b Pfi W h / MSD S h i Pl h / T k d N d
246 895 patients (vs 249 704 en
2010)
• 32 965 centers (vs 24 337 en 2010)
and merger between Pfizer-Wyeth / MSD-Schering Plough / Takeda-Nycomed
8
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

9. US‐Canada has increased significantly as they are now
involved in nearly 4 studies out of 5involved in nearly 4 studies out of 5
Trial distribution per year and per region W ldTrial distribution per year and per region
(Europe 100 %)
World
90%
100%
Latine Am.
67%
62%
66%
79%
70%
80%
90%
36%
42%
3 %
40%
40% 45%
40%
50%
60%
Asia
37%
40%
19%
35%
20%
30%
%
USA/Canada
0%
10%
2004 2006 2008 2010 2012
9
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

10. In Europe, participation of Western European countries is
quite close, in overall decrease
Average Number of patients per center and per year EAverage Number of patients per center and per year Europe
13,0
Scandinavia
9,4
9,6
13,1
9,7
7,8 8,3
11,0Germany
6,3
, 8,3
6,6
6,36,5
8,1
6,3
7,2
8,1
6,7
6,6
7,0
9,0
Spain
France
,
4 8
5,26,3 7,6
6,3
4,8
5,6
4,8
7,8
5,2
4,0
5,0
United Kingdom
Italy
Only studies involving France have been included
4,8
3,0
2004 2006 2008 2010 2012
10
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

11. At the European level, the analysis per phase revealed a higher
rate of phase II studies in France
Only studies involving France were included
rate of phase II studies in France
Phase II and III distribution (2012)Phase II and III distribution (2012)
Number
of
studies
296 245 402 246 197 181
27% 27%
33% 30%
24% 22%
Phase II
Phase III
73% 73%
67% 70%
76% 78%
B t ith hi h ti f h III t di i h t
Germany Spain France Italy United Kingdom Scandinavia
 But with a higher proportion of phase III studies in each country
 Involvement of France in Oncology and Rare Diseases Phase II
11Synthesis of 6 surveys conducted by Leem since 2002 and 2012

12. Variations in timelines approval from the different
authorities are different
M di ti li t bt i th l b M di ti li t bt i th l b
authorities are different
Median timelines to obtain the approval by
ANSM (in days)
Median timelines to obtain the approval by
EC (in days)
+6%
-12,5%
+6%
Not
analyzedanalyzed
Phase I, II, III and IV for regulatory purpose
12
g y p p
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

13. Hospital contracts (first contract) timelines dropped
significantly from 2006 to 2010 and have since remained
stablestable
Median deadline to obtain the signature of the first hospital
contract (in days)
-
11%11% -
10%
13
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

14. France recruited 6.5 % of total patients and ranks behind
USA Eastern Europe Asia Latin America but also GermanyUSA, Eastern Europe, Asia, Latin America but also Germany
 As only studies involving France were
included, the number of studies
Number of patients Ratio recruited
patients/
1 000 000 hab
Number of
studies Number % ,
France took part in is the highest by
definition
In comparison with the 2010 survey
France 420 US  47 333 19,2% 153
Germany 310 Est Europe  36 970 15,0% 113
Other West. Eur 301 Asia  25 368 10,3% 7
In comparison with the 2010 survey
 An increase for:
 The USA : 19,2% vs 15,4%
 Asia: 10,3% vs 7,8%
A d f E % 6 8%
US 293 Germany = 22 047 8,9% 270
Est Europe 280 Latin Am. 20 743 8,4% 293
Italy 258 Other West. Eur 19 930 8,1% 39
Spain 257 France  16 092 6,5% 246
Canada 237 Canada 10 847 4,4% 317
 A decrease for Europe: 52,9% vs 60,8%
 No variation for Germany : 8,9% vs 9%
 Also a decrease for:
 Eastern Europe: 15,0% vs 21,6%
% %
, %
Australasia 215 Scandinavia 10 770 4,4% 423
United Kingdom 207 Spain 9 672 3,9% 206
Asia 191 Australasia 8 761 3,5% 114
Scandinavia 188 Italy 8 029 3,3% 133
U i d Ki d  France : 6,5% vs 7,6%Latin Am. 166 United Kingdom 7 048 2,9% 17
Africa and
Mid.East. 119 Afr. Moyen Or. 3 285 1,3% 55
Europe 420 130 558 52,9% 177
World 420 246 895 100% 45
14
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

15. Conclusion of the 2012 survey
 Gl b l d f E i i t ti l titi Global decrease of Europe in international competition
 France remains in the average of the European countries at a growing
distance from Germany, but still with some advantagesy g
 Some alarming signals which calls for the mobilization of all
stakeholdersstakeholders
 Collapse of some therapeutic areas
 EC and Hospital contracts timelines
 Deterioration of the perception of administrative simplicity
15
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

16. Reinforce our mobilization efforts at all levelsReinforce our mobilization efforts at all levels
 A mobilization of all Member States and of the European
C i iCommission
 To adopt an European Regulation which really simplifies processes and
shortens timelines
 To set up a positive environment for clinical research, in particular a
reflection on a European certified training for investigators
A b tt f i F A better focus in France
 Hospitals for a simplification of hospitals contractualization and the
setting up of efficient organizations (CenGeps actions)g p g p
 Regulatory Authorities (ANSM, EC) to keep competitive timelines
 Investigators to improve feasibility studies and GCP training
 Patients to favor their inclusion in clinical trials
16
Synthesis of 6 surveys conducted by Leem since 2002 and 2012

17. Pharmacist Industrial Vision of Clinical trialsPharmacist Industrial Vision of Clinical trials
Vision of International Clinical Research (Leem Study)
Thanks for your attention
JP PACCIONI EIPG April 11th, 2014