Session 13 harald_heemstra
16
Date: Prepared for: Prepared by: Pharmerit BV Marten Meesweg 105 3068 AV Rotterdam The Netherlands www.pharmerit.com +31 (0) 10 451 9924 Predictors of orphan drug approval 15 May 2010 Xxx Xxx Xxx Company X Company X Company X [email protected] Harald Heemstra, PhD Harald E. Heemstra, PhD [email protected] European Conference on Rare Diseases Krakow, 15 May 2010
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Transcript of Session 13 harald_heemstra
Date:
Prepared for:
Prepared by:
Pharmerit BVMarten Meesweg 1053068 AV RotterdamThe Netherlandswww.pharmerit.com+31 (0) 10 451 9924
Predictors of orphan drug approval
15 May 2010
Xxx
Xxx
Xxx
Company X
Company X
Company X
[email protected] Heemstra, PhD
Harald E. Heemstra, [email protected]
European Conference on Rare DiseasesKrakow, 15 May 2010
2
Introduction
Utrecht Institute for Pharmaceutical Sciences
Dutch Steering Committee on Orphan Drugs
3
Aim of the presentation
To discuss predictors of successfully obtaining
marketing authorization for orphan drugs in the
European Union or the United States
Based on the results of two studies
4
Orphan drugs EU US
Market exclusivity 10 years 7 years
Protocol assistance Yes Yes
Reduction of regulatory fees Yes Yes
50% tax credit for clinical studies No Yes
Dedicated subsidies for clinical studies No Yes
Regulation (EC) No. 141/2000 of the European Parliament and of the Council The Orphan Drug Act. United States Public Law No 97-414. 1983
Incentive measures for orphan drugs
in the EU and the US
5
The three stage process to patient
access
Orphandesignation
Marketingauthorization
Market Access National authorities decide
Differences in access and reimbursement throughout the EU
Centralised procedure mandatory for designated orphan drugs
Authorisation valid throughout the EU
Only designation as potential OD
No marketing authorization
6
2000 2001 2002 2003 2004 2005 2006 2007 2008 20090
20
40
60
80
100
120
12
4135
46
61
78
69
95
73
105
0 3 4 5 6 38
136
11
Orphan designations Authorized Orphan Medicinal products
Orphan drug development in the EU
#ODs=8.8*y + 13.3 (R2=0.87) #authorized ODs=1.0*y + 0.6 (R2=0.76)
www.ema.europa.eu
7
2000 2001 2002 2003 2004 2005 2006 2007 2008 20090
20
40
60
80
100
120
140
160
180
6571
55
88
123117
135
116
164 160
5 510 11 12 12 11 15 13
18
Orphan designations Authorized Orphan Drugs
#authorized ODs=1.2*y + 4.6 (R2=0.83)
Orphan drug development in the US
#ODs=11.8*y + 44.5 (R2=0.86)
www.fda.gov/orphan
8
Is orphan drug development in the EU
lagging behind the US?
US 1983-1992
US 2000-2009
EU 2000-2009
0 200 400 600 800 1000 1200
359
1094
615
73
112
59
Authorized Orphan Medicinal Products [2]Orphan designations [1]
1Designations active at April 2010 only2Corrected for indication extensions
9
Orphan drug development in Europe;
three phases
Adapted from: Leufkens, Epposi 2007
Increasing awareness
Increasing number of orphan designations
Increasing criticism: • Low number of authorized
orphan drugs• High costs
2000 2005
I.
II.
III.
10
Slow development of an orphan designated product into
an approved product
Low quality of the clinical development program
Poor documentation
Many uncontroled trials / small sample sizes
Criticism on the speed of orphan drug
development in the EU
Joppi et al. Br J Clin Pharmacol 2009
11
Design of the study
Comparison of authorized EU orphan drugs (cases) with designated products (controls)
Study period: Jan 2000-Oct 2006Case control design
Controls are matched 1:3 on date of designationControls are sampled from total cohort (n=386)
Public domain data
Comparison of the products on three groups of characteristics:
Characteristics of the indicationCharacteristics of the productCharacteristics of the sponsor
A1 A2 … A36
2000 D1a/D1b/D1c D2a/D2b/D2c … Dxa/Dxb/Dxc 2006
12
Predictors of orphan drug
development in the EU
Case (n=36)
Control (n=60) OR (95% CI)
Experience of the sponsor
Other products approved 31 26 11.5 (3.2-42.2)
Other orphan drugs designated 30 28 8.0 (2.5-25.7)
Other orphan drugs approved 28 13 16.2 (5.5-47.4)
Indication group
Metabolism (vs. oncology) 9 5 3.6 (1.0-12.4)
Pharmaceutical formulation
Oral (vs. parenteral) 21 12 4.0 (1.5-10.6)
Type of product
Existing synthetic molecules (vs. biologics)
15 15 3.3 (1.1-10.6)
Previously authorised 8 4 4.0 (1.1-14.5)
3.9 (0.9-16.6)
17.3 (5.6-53.1)
13
Follow-up studies including FDA and
EMA data
Region Data source Time Characteristics included
EUPublic domain
2000-2006
•Indication characteristics•Product characteristics•Sponsor characteristics
US
Public domain + FDA data
1998-2007
•Indication characteristics•Product characteristics•Sponsor characteristics•Interaction characteristics•Clinical trial program characteristics
EUPublic domain + EMEA data
2000-2009
14
Predictors of orphan drug failure in the
US
Interaction and dialogue with regulatory authorities
Scientific advice / guidance meetings
Discuss and agree on the design issues of the
clinical trials
Comply to outcomes of these discussions
Informal at meetings/conferences
Design of the pivotal trial:
Endpoint selection
Choice of target population
15
Experience
Sponsor
Drug substance/formulation
Interaction with regulatory authorities
Consensus and compliance to agreements on
trial design
Careful design of the clinical trial
Endpoint selection
Target population
Take home message: predictors for
successful orphan drug development
